This document provides an overview of monoclonal antibodies (MAbs), including their definition, introduction, pharmacology, adverse effects, and therapeutic potentials. Some key points include:
- MAbs are antibodies produced from a single clone that are more abundant and uniform than natural antibodies.
- They have specific mechanisms of action including blocking target antigens, inducing cytotoxicity, and inhibiting growth factors.
- Therapeutic areas include immunosuppression, autoimmune diseases, cancer, and infectious diseases. MAbs targeting tumor necrosis factor alpha have shown promise for treating rheumatoid arthritis and Crohn's disease.
Monoclonal antibodies can be used in cancer therapy in several ways:
1) They can bind to cancer cell antigens and recruit the immune system to attack the cancer cells or block growth signaling pathways.
2) They can be conjugated to toxins, enzymes, or radioisotopes to directly kill cancer cells after binding.
3) By inhibiting immune checkpoint proteins like CTLA-4 and PD-1, they can enhance the immune system's antitumor response.
4) Examples of monoclonal antibodies used in cancer include rituximab for blood cancers, trastuzumab for HER2-positive breast cancer, and immune checkpoint inhibitors like nivolumab and pembrolizumab.
This document discusses the use of monoclonal antibodies for cancer therapy. It provides background on conventional chemotherapy and highlights limitations. It then covers the history and development of monoclonal antibodies, including their production and mechanisms of targeting cancer cells, such as antigen cross-linking, activating death receptors, and delivering cytotoxic agents. Specific examples of toxin-immunoconjugates and antibody-directed enzyme prodrug therapy are described. The mechanism and applications of the monoclonal antibody Rituximab for lymphoma are discussed. In conclusion, the document notes the potential for optimizing monoclonal antibody combinations with chemotherapy and radiation therapy.
The document discusses monoclonal antibodies, including their discovery, structure, functions, types, production, targets for cancer treatment, and mechanisms of action. It provides details on how monoclonal antibodies can directly kill tumor cells or induce immune-mediated killing through mechanisms like phagocytosis, complement activation, and antibody-dependent cell cytotoxicity. The document also examines immune checkpoint inhibitors, immunotoxins, bispecific antibodies, immunoliposomes, antibody fragments, and an animal model study on monoclonal antibody treatment for colorectal cancer.
Monoclonal Antibodies for Cancer TreatmentMannoj Subedi
Monoclonal antibodies (mAbs) are identical antibodies generated from a single B-cell clone that recognize a unique binding site on a single antigen. There are several types of mAbs including murine, chimeric, humanized, and human. mAbs can be used to treat cancer through immunoconjugated mAbs, bispecific antibodies, and naked monoclonal antibodies. Common side effects of mAb treatment include dizziness, headaches, and allergies while more severe side effects can involve bleeding, blood clots, and autoimmune disorders. Advances in genetic engineering have improved mAb design and effectiveness.
Monoclonal antibodies in cancer treatment By Ankit TribhuvaneMumbai University
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that specifically bind to target cells. They can be used for cancer therapy by triggering immune system attacks on cancer cells, blocking growth signals, or preventing new blood vessel formation. Monoclonal antibodies are produced through hybridoma technology, fusing B cells with myeloma cells. This produces immortal clones that secrete identical antibodies. Monoclonal antibodies have applications in cancer diagnosis and treatment, with therapeutic antibodies targeting tumors through mechanisms like antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.
Monoclonal antibodies have potential as anti-cancer therapies by specifically targeting tumor cells. They can induce apoptosis through several mechanisms, including antigen cross-linking, activating death receptors, or delivering cytotoxic agents directly to tumors. Challenges include insufficient drug delivery to solid tumors and heterogeneous antigen expression limiting targeted cells. New strategies involve using monoclonal antibodies to activate enzymes that convert locally administered pro-drugs into anti-tumor agents at the tumor site. The first approved therapeutic monoclonal antibody Rituximab treats B-cell lymphomas with high response rates. Future research aims to optimize combinations with chemotherapy and determine best candidates.
Monoclonal Antibodies As Therapeutic Agents In Oncology Anddrmisbah83
This document discusses monoclonal antibodies as therapeutic agents for cancer and antibody gene therapy. It describes how monoclonal antibodies work to target cancer cells, lists some common monoclonal antibody drugs approved for cancer treatment, and discusses potential side effects. It also introduces the concept of using antibody gene therapy as a new strategy for cancer treatment by delivering antibody genes directly to tumors using vectors like adenovirus or mesenchymal stem cells.
This document discusses immunotherapeutics and immunity. It defines immunity as the body's ability to protect itself from infectious disease. There are two main types of immunity: innate and adaptive. Immunotherapy involves stimulating, enhancing, suppressing, or desensitizing the immune system to treat or prevent disease like cancer or autoimmune disorders. The document outlines various immunotherapeutic approaches including immunostimulants, monoclonal antibodies, antibody-directed enzyme prodrug therapy, immunotoxins, and immunomodulators like adaptive cell therapy and cancer vaccines.
Monoclonal antibodies can be used in cancer therapy in several ways:
1) They can bind to cancer cell antigens and recruit the immune system to attack the cancer cells or block growth signaling pathways.
2) They can be conjugated to toxins, enzymes, or radioisotopes to directly kill cancer cells after binding.
3) By inhibiting immune checkpoint proteins like CTLA-4 and PD-1, they can enhance the immune system's antitumor response.
4) Examples of monoclonal antibodies used in cancer include rituximab for blood cancers, trastuzumab for HER2-positive breast cancer, and immune checkpoint inhibitors like nivolumab and pembrolizumab.
This document discusses the use of monoclonal antibodies for cancer therapy. It provides background on conventional chemotherapy and highlights limitations. It then covers the history and development of monoclonal antibodies, including their production and mechanisms of targeting cancer cells, such as antigen cross-linking, activating death receptors, and delivering cytotoxic agents. Specific examples of toxin-immunoconjugates and antibody-directed enzyme prodrug therapy are described. The mechanism and applications of the monoclonal antibody Rituximab for lymphoma are discussed. In conclusion, the document notes the potential for optimizing monoclonal antibody combinations with chemotherapy and radiation therapy.
The document discusses monoclonal antibodies, including their discovery, structure, functions, types, production, targets for cancer treatment, and mechanisms of action. It provides details on how monoclonal antibodies can directly kill tumor cells or induce immune-mediated killing through mechanisms like phagocytosis, complement activation, and antibody-dependent cell cytotoxicity. The document also examines immune checkpoint inhibitors, immunotoxins, bispecific antibodies, immunoliposomes, antibody fragments, and an animal model study on monoclonal antibody treatment for colorectal cancer.
Monoclonal Antibodies for Cancer TreatmentMannoj Subedi
Monoclonal antibodies (mAbs) are identical antibodies generated from a single B-cell clone that recognize a unique binding site on a single antigen. There are several types of mAbs including murine, chimeric, humanized, and human. mAbs can be used to treat cancer through immunoconjugated mAbs, bispecific antibodies, and naked monoclonal antibodies. Common side effects of mAb treatment include dizziness, headaches, and allergies while more severe side effects can involve bleeding, blood clots, and autoimmune disorders. Advances in genetic engineering have improved mAb design and effectiveness.
Monoclonal antibodies in cancer treatment By Ankit TribhuvaneMumbai University
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that specifically bind to target cells. They can be used for cancer therapy by triggering immune system attacks on cancer cells, blocking growth signals, or preventing new blood vessel formation. Monoclonal antibodies are produced through hybridoma technology, fusing B cells with myeloma cells. This produces immortal clones that secrete identical antibodies. Monoclonal antibodies have applications in cancer diagnosis and treatment, with therapeutic antibodies targeting tumors through mechanisms like antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.
Monoclonal antibodies have potential as anti-cancer therapies by specifically targeting tumor cells. They can induce apoptosis through several mechanisms, including antigen cross-linking, activating death receptors, or delivering cytotoxic agents directly to tumors. Challenges include insufficient drug delivery to solid tumors and heterogeneous antigen expression limiting targeted cells. New strategies involve using monoclonal antibodies to activate enzymes that convert locally administered pro-drugs into anti-tumor agents at the tumor site. The first approved therapeutic monoclonal antibody Rituximab treats B-cell lymphomas with high response rates. Future research aims to optimize combinations with chemotherapy and determine best candidates.
Monoclonal Antibodies As Therapeutic Agents In Oncology Anddrmisbah83
This document discusses monoclonal antibodies as therapeutic agents for cancer and antibody gene therapy. It describes how monoclonal antibodies work to target cancer cells, lists some common monoclonal antibody drugs approved for cancer treatment, and discusses potential side effects. It also introduces the concept of using antibody gene therapy as a new strategy for cancer treatment by delivering antibody genes directly to tumors using vectors like adenovirus or mesenchymal stem cells.
This document discusses immunotherapeutics and immunity. It defines immunity as the body's ability to protect itself from infectious disease. There are two main types of immunity: innate and adaptive. Immunotherapy involves stimulating, enhancing, suppressing, or desensitizing the immune system to treat or prevent disease like cancer or autoimmune disorders. The document outlines various immunotherapeutic approaches including immunostimulants, monoclonal antibodies, antibody-directed enzyme prodrug therapy, immunotoxins, and immunomodulators like adaptive cell therapy and cancer vaccines.
Cancer is caused by abnormal cell growth that can spread to other parts of the body. Immunotherapy is a type of cancer treatment that boosts the immune system to fight cancer. It works by activating innate and adaptive immune responses using substances made by the body or in a lab. Major types of immunotherapy include monoclonal antibody therapy, cancer vaccines, and immune checkpoint inhibitors which help the immune system better detect and destroy cancer cells.
Cancer immunotherapy nivedita shah msc.biotech- 13937eureka1
This document provides an overview of cancer immunotherapy. It discusses how immunotherapy harnesses the immune system to fight cancer through techniques like monoclonal antibodies, cytokines, adoptive cell therapy, and cancer vaccines. Monoclonal antibodies target specific antigens on cancer cells, while cytokines are proteins that serve as messenger molecules between immune cells. Adoptive cell therapy transfers immune cells back into patients to improve immune function against tumors. Cancer vaccines stimulate the immune system to attack existing or prevent future cancer cells. The document also outlines some limitations of immunotherapy approaches and notes how cancer immunotherapy was named Breakthrough of the Year by the journal Science in 2013.
This document summarizes various targeted anticancer therapies. It discusses targeted therapies that interfere with molecular structures implicated in tumor growth like nuclear factors, cell survival factors, and angiogenesis factors. Primary targeted therapy tools are monoclonal antibodies and small synthetic molecules. Protein kinases and their role in signaling pathways are described. Examples of targeted therapies discussed include BCR-ABL tyrosine kinase inhibitors, EGFR inhibitors, HER2/NEU inhibitors, angiogenesis inhibitors targeting VEGF, mTOR inhibitors, proteasome inhibitors, MAPK pathway inhibitors, and monoclonal antibodies. Resistance mechanisms and newer agents to overcome resistance are also summarized.
This document summarizes screening methods for immunomodulators. It describes in vitro and in vivo methods for testing immunological factors. Some key in vitro methods discussed include inhibition of histamine release from mast cells and mitogen-induced lymphocyte proliferation assays. Key in vivo models described are the anti-anaphylactic activity (Schultz-Dale reaction) assay and delayed type hypersensitivity testing in sensitized animals. The document also provides details on the procedures and evaluations for some of these screening methods.
This document discusses monoclonal antibodies, including their discovery and types. It provides details on:
- George Kohler and Cesar Milstein discovered hybridoma technology in 1975, which enables the production of monoclonal antibodies from a single clone of B cells.
- There are four main types of monoclonal antibodies based on their origin: murine, chimeric, humanized, and fully human. Hybridoma technology fuses B cells with myeloma cells to produce monoclonal antibodies indefinitely in culture.
- Monoclonal antibodies can be "naked" or conjugated to drugs, toxins, or radioactive particles to target cancers. They work by binding to specific antigens on cells and triggering immune responses or delivering cytotoxic payloads to targeted
Monoclonal antibodies (mAbs) have various applications including diagnostic, therapeutic, and catalytic uses. Diagnostically, mAbs allow rapid diagnosis of diseases through detection of antigens. Therapeutically, mAbs can treat cancer by directly binding to cancer cells, delivering toxins or radiation to cancer cells, or blocking growth signals. FDA-approved mAbs for cancer treatment include Rituximab and Trastuzumab. Conjugated mAbs can deliver toxins or radiation specifically to tumor cells. mAbs are also used to treat autoimmune diseases and for organ transplant rejection. Catalytically, some mAbs exhibit enzyme-like effects and are known as abzymes.
Humanisation of antibodies & immunotherapeutics in clinical practice Aaqib Naseer
This document discusses humanization of monoclonal antibodies and immunotherapeutics used in clinical practice. It describes the techniques used to humanize antibodies, including CDR grafting, phage display, and transgenic animals. It then discusses various immunotherapeutics used clinically such as monoclonal antibodies, cytokines, cancer vaccines, and cell-based therapies. Monoclonal antibodies target specific antigens on cancer cells and can be naked or conjugated. Checkpoint inhibitors like anti-CTLA-4 and anti-PD-1 antibodies work by releasing brakes on the immune system. Cytokines such as interferons and interleukins modulate immune responses. Cancer vaccines aim to stimulate immunity against tumor antigens.
This document discusses the use of monoclonal antibodies in cancer treatment. It begins by introducing monoclonal antibodies and their benefits over conventional chemotherapy, including homogeneity, specificity, fewer side effects, and the ability to be tagged with other compounds. It then describes naked monoclonal antibodies that work alone and conjugated monoclonal antibodies that are joined to chemotherapy drugs or radioactive particles. Several FDA-approved monoclonal antibodies for different cancer types are listed. The mechanisms of action of rituximab, trastuzumab emtansine, and other monoclonal antibodies are described. Current clinical trials and limitations of monoclonal antibody therapy are also summarized.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
Immuno-Oncology: An Evolving Approach to Cancer Care
Review a downloadable slide deck by Thomas F. Gajewski, MD, PhD, covering the most clinically relevant new data reported from Immuno-Oncology: An Evolving Approach to Cancer Care.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Format: Microsoft PowerPoint (.ppt) | File size: 26.2 MB | Date posted: 6/20/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of June 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
The document summarizes information about monoclonal antibodies (mAbs), including their definition as identical antibodies generated from a single B cell clone that target a single epitope. It describes the advantages of mAbs such as specificity and applications in treatment. The document outlines the preparation process for mAbs and different types including murine, chimeric, humanized, and fully human. It discusses uses of mAbs in diagnosis, therapy, and protein purification and some challenges and future prospects.
Monoclonal antibodies (mAbs) are identical antibodies produced by a single clone of immune cells that recognize a specific antigen. There are three main mechanisms by which mAbs can treat cancer: 1) directly inducing apoptosis or inhibiting growth of cancer cells by binding to antigens, 2) delivering toxins, radioisotopes or cytokines to cancer cells when modified for drug delivery, and 3) using bispecific antibodies to bind cancer antigens and effector cells to elicit an immune response. Common mAbs approved by the FDA for cancer treatment target growth factor receptors or directly elicit apoptotic signaling in cancer cells. Production of mAbs is primarily through hybridoma technology fusing antibody-producing cells with myeloma cells.
The document discusses various aspects of antimicrobial drug resistance. It begins by defining antimicrobial drugs and antimicrobial resistance. It then covers the genetic basis of resistance including chromosome-mediated resistance, plasmid-mediated resistance, and transposon-mediated resistance. Specific mechanisms of resistance to different drug classes such as penicillins, cephalosporins, carbapenems, and quinolones are described. Non-genetic bases of resistance and methods to test antibiotic sensitivity and combat resistance are also summarized.
A talk presented by Prof. Mohamed Labib Salem at Minofia University محاضرة للأستاذ الدكتور محمد لبيب سالم جامعة طنطا يوم الثلاثاء السادس عشر من فبراير بجامعة المنوفية
Monoclonal antibodies (mAbs) are monospecific antibodies produced by a single clone of cells. They have specific structures and functions that allow them to recognize antigens and induce immune responses. mAbs are produced using hybridoma technology and have evolved from murine to humanized and human forms to reduce immunogenicity. They are used widely in treatment of diseases like cancer, autoimmune disorders, transplant rejection and infections.
Monoclonal antibodies are produced by identical immune cells that recognize a specific antigen. They have various applications including drug delivery, diagnostics, and cancer therapy. For drug delivery, monoclonal antibodies can be conjugated to chemotherapeutic agents or toxins to target cancer cells. Naked monoclonal antibodies directly bind to tumor antigens to induce immune responses. Advances include developing humanized monoclonal antibodies and nanobodies for oral administration to expand therapeutic applications. Monoclonal antibodies are an important class of drugs in oncology and other areas with a large and growing global market.
Production of monoclonal antibodies and applications in therapy and diagnosisAhmed Madni
Monoclonal antibodies are identical antibodies produced by a single clone of cells that bind to a specific epitope. They are produced through the fusion of antibody-producing B cells with myeloma cells, generating hybridoma cells that can produce antibodies indefinitely. Monoclonal antibodies have applications in therapy and diagnosis, including detecting antigens through techniques like ELISA, purifying proteins, and treating cancers by delivering toxins or radioisotopes to tumor cells. Advances in engineering have reduced issues like human anti-mouse antibody responses by creating chimeric or humanized antibodies.
The document discusses current strategies for cancer immunotherapy, including monoclonal antibodies and cell-based immunotherapy. Monoclonal antibodies can target cancer cells directly via mechanisms like antibody-dependent cellular cytotoxicity. They can also be conjugated to toxins or radioactive particles for targeted delivery. Immune checkpoint blockers are a type of monoclonal antibody that blocks inhibitory receptors on T-cells to prolong anti-tumor responses. Cell-based immunotherapy includes adoptive T-cell therapy using tumor-infiltrating lymphocytes or chimeric antigen receptor T-cells that are genetically modified to target specific tumor antigens. Immunotherapy has advantages over other treatments in that it can target cancers throughout the body, is highly specific to cancer cells, and may provide durable, long-
This document discusses monoclonal antibodies (mAbs), including their structure, production, types, and mechanisms of action. Some key points:
- mAbs are laboratory-produced molecules that can mimic the immune system's attack on cancer cells by binding to antigens on cancer surfaces.
- There are four types of mAbs based on their source: murine, chimeric, humanized, and human. Murine mAbs come from mice while human mAbs are fully human.
- mAbs can directly kill cancer cells, induce immune-mediated killing, or block blood vessel growth to tumors.
- Production involves immunizing an animal, fusing lymphocytes with myeloma cells, selecting antibody-producing hybridomas
Cancer is caused by abnormal cell growth that can spread to other parts of the body. Immunotherapy is a type of cancer treatment that boosts the immune system to fight cancer. It works by activating innate and adaptive immune responses using substances made by the body or in a lab. Major types of immunotherapy include monoclonal antibody therapy, cancer vaccines, and immune checkpoint inhibitors which help the immune system better detect and destroy cancer cells.
Cancer immunotherapy nivedita shah msc.biotech- 13937eureka1
This document provides an overview of cancer immunotherapy. It discusses how immunotherapy harnesses the immune system to fight cancer through techniques like monoclonal antibodies, cytokines, adoptive cell therapy, and cancer vaccines. Monoclonal antibodies target specific antigens on cancer cells, while cytokines are proteins that serve as messenger molecules between immune cells. Adoptive cell therapy transfers immune cells back into patients to improve immune function against tumors. Cancer vaccines stimulate the immune system to attack existing or prevent future cancer cells. The document also outlines some limitations of immunotherapy approaches and notes how cancer immunotherapy was named Breakthrough of the Year by the journal Science in 2013.
This document summarizes various targeted anticancer therapies. It discusses targeted therapies that interfere with molecular structures implicated in tumor growth like nuclear factors, cell survival factors, and angiogenesis factors. Primary targeted therapy tools are monoclonal antibodies and small synthetic molecules. Protein kinases and their role in signaling pathways are described. Examples of targeted therapies discussed include BCR-ABL tyrosine kinase inhibitors, EGFR inhibitors, HER2/NEU inhibitors, angiogenesis inhibitors targeting VEGF, mTOR inhibitors, proteasome inhibitors, MAPK pathway inhibitors, and monoclonal antibodies. Resistance mechanisms and newer agents to overcome resistance are also summarized.
This document summarizes screening methods for immunomodulators. It describes in vitro and in vivo methods for testing immunological factors. Some key in vitro methods discussed include inhibition of histamine release from mast cells and mitogen-induced lymphocyte proliferation assays. Key in vivo models described are the anti-anaphylactic activity (Schultz-Dale reaction) assay and delayed type hypersensitivity testing in sensitized animals. The document also provides details on the procedures and evaluations for some of these screening methods.
This document discusses monoclonal antibodies, including their discovery and types. It provides details on:
- George Kohler and Cesar Milstein discovered hybridoma technology in 1975, which enables the production of monoclonal antibodies from a single clone of B cells.
- There are four main types of monoclonal antibodies based on their origin: murine, chimeric, humanized, and fully human. Hybridoma technology fuses B cells with myeloma cells to produce monoclonal antibodies indefinitely in culture.
- Monoclonal antibodies can be "naked" or conjugated to drugs, toxins, or radioactive particles to target cancers. They work by binding to specific antigens on cells and triggering immune responses or delivering cytotoxic payloads to targeted
Monoclonal antibodies (mAbs) have various applications including diagnostic, therapeutic, and catalytic uses. Diagnostically, mAbs allow rapid diagnosis of diseases through detection of antigens. Therapeutically, mAbs can treat cancer by directly binding to cancer cells, delivering toxins or radiation to cancer cells, or blocking growth signals. FDA-approved mAbs for cancer treatment include Rituximab and Trastuzumab. Conjugated mAbs can deliver toxins or radiation specifically to tumor cells. mAbs are also used to treat autoimmune diseases and for organ transplant rejection. Catalytically, some mAbs exhibit enzyme-like effects and are known as abzymes.
Humanisation of antibodies & immunotherapeutics in clinical practice Aaqib Naseer
This document discusses humanization of monoclonal antibodies and immunotherapeutics used in clinical practice. It describes the techniques used to humanize antibodies, including CDR grafting, phage display, and transgenic animals. It then discusses various immunotherapeutics used clinically such as monoclonal antibodies, cytokines, cancer vaccines, and cell-based therapies. Monoclonal antibodies target specific antigens on cancer cells and can be naked or conjugated. Checkpoint inhibitors like anti-CTLA-4 and anti-PD-1 antibodies work by releasing brakes on the immune system. Cytokines such as interferons and interleukins modulate immune responses. Cancer vaccines aim to stimulate immunity against tumor antigens.
This document discusses the use of monoclonal antibodies in cancer treatment. It begins by introducing monoclonal antibodies and their benefits over conventional chemotherapy, including homogeneity, specificity, fewer side effects, and the ability to be tagged with other compounds. It then describes naked monoclonal antibodies that work alone and conjugated monoclonal antibodies that are joined to chemotherapy drugs or radioactive particles. Several FDA-approved monoclonal antibodies for different cancer types are listed. The mechanisms of action of rituximab, trastuzumab emtansine, and other monoclonal antibodies are described. Current clinical trials and limitations of monoclonal antibody therapy are also summarized.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
Immuno-Oncology: An Evolving Approach to Cancer Care
Review a downloadable slide deck by Thomas F. Gajewski, MD, PhD, covering the most clinically relevant new data reported from Immuno-Oncology: An Evolving Approach to Cancer Care.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Format: Microsoft PowerPoint (.ppt) | File size: 26.2 MB | Date posted: 6/20/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of June 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
The document summarizes information about monoclonal antibodies (mAbs), including their definition as identical antibodies generated from a single B cell clone that target a single epitope. It describes the advantages of mAbs such as specificity and applications in treatment. The document outlines the preparation process for mAbs and different types including murine, chimeric, humanized, and fully human. It discusses uses of mAbs in diagnosis, therapy, and protein purification and some challenges and future prospects.
Monoclonal antibodies (mAbs) are identical antibodies produced by a single clone of immune cells that recognize a specific antigen. There are three main mechanisms by which mAbs can treat cancer: 1) directly inducing apoptosis or inhibiting growth of cancer cells by binding to antigens, 2) delivering toxins, radioisotopes or cytokines to cancer cells when modified for drug delivery, and 3) using bispecific antibodies to bind cancer antigens and effector cells to elicit an immune response. Common mAbs approved by the FDA for cancer treatment target growth factor receptors or directly elicit apoptotic signaling in cancer cells. Production of mAbs is primarily through hybridoma technology fusing antibody-producing cells with myeloma cells.
The document discusses various aspects of antimicrobial drug resistance. It begins by defining antimicrobial drugs and antimicrobial resistance. It then covers the genetic basis of resistance including chromosome-mediated resistance, plasmid-mediated resistance, and transposon-mediated resistance. Specific mechanisms of resistance to different drug classes such as penicillins, cephalosporins, carbapenems, and quinolones are described. Non-genetic bases of resistance and methods to test antibiotic sensitivity and combat resistance are also summarized.
A talk presented by Prof. Mohamed Labib Salem at Minofia University محاضرة للأستاذ الدكتور محمد لبيب سالم جامعة طنطا يوم الثلاثاء السادس عشر من فبراير بجامعة المنوفية
Monoclonal antibodies (mAbs) are monospecific antibodies produced by a single clone of cells. They have specific structures and functions that allow them to recognize antigens and induce immune responses. mAbs are produced using hybridoma technology and have evolved from murine to humanized and human forms to reduce immunogenicity. They are used widely in treatment of diseases like cancer, autoimmune disorders, transplant rejection and infections.
Monoclonal antibodies are produced by identical immune cells that recognize a specific antigen. They have various applications including drug delivery, diagnostics, and cancer therapy. For drug delivery, monoclonal antibodies can be conjugated to chemotherapeutic agents or toxins to target cancer cells. Naked monoclonal antibodies directly bind to tumor antigens to induce immune responses. Advances include developing humanized monoclonal antibodies and nanobodies for oral administration to expand therapeutic applications. Monoclonal antibodies are an important class of drugs in oncology and other areas with a large and growing global market.
Production of monoclonal antibodies and applications in therapy and diagnosisAhmed Madni
Monoclonal antibodies are identical antibodies produced by a single clone of cells that bind to a specific epitope. They are produced through the fusion of antibody-producing B cells with myeloma cells, generating hybridoma cells that can produce antibodies indefinitely. Monoclonal antibodies have applications in therapy and diagnosis, including detecting antigens through techniques like ELISA, purifying proteins, and treating cancers by delivering toxins or radioisotopes to tumor cells. Advances in engineering have reduced issues like human anti-mouse antibody responses by creating chimeric or humanized antibodies.
The document discusses current strategies for cancer immunotherapy, including monoclonal antibodies and cell-based immunotherapy. Monoclonal antibodies can target cancer cells directly via mechanisms like antibody-dependent cellular cytotoxicity. They can also be conjugated to toxins or radioactive particles for targeted delivery. Immune checkpoint blockers are a type of monoclonal antibody that blocks inhibitory receptors on T-cells to prolong anti-tumor responses. Cell-based immunotherapy includes adoptive T-cell therapy using tumor-infiltrating lymphocytes or chimeric antigen receptor T-cells that are genetically modified to target specific tumor antigens. Immunotherapy has advantages over other treatments in that it can target cancers throughout the body, is highly specific to cancer cells, and may provide durable, long-
This document discusses monoclonal antibodies (mAbs), including their structure, production, types, and mechanisms of action. Some key points:
- mAbs are laboratory-produced molecules that can mimic the immune system's attack on cancer cells by binding to antigens on cancer surfaces.
- There are four types of mAbs based on their source: murine, chimeric, humanized, and human. Murine mAbs come from mice while human mAbs are fully human.
- mAbs can directly kill cancer cells, induce immune-mediated killing, or block blood vessel growth to tumors.
- Production involves immunizing an animal, fusing lymphocytes with myeloma cells, selecting antibody-producing hybridomas
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that recognize a specific epitope on an antigen. They are produced through the fusion of B cells from an immunized animal with myeloma cells to form a hybridoma. This hybridoma will continuously secrete the same monoclonal antibody. Monoclonal antibodies have various diagnostic and therapeutic applications including use in biochemical assays, diagnostic imaging, cancer treatment, and protein purification due to their high specificity for targets.
This document provides an overview of monoclonal antibodies and gene therapy. It discusses the discovery of monoclonal antibodies by Kohler and Milstein in 1975. It also describes the multi-step process of producing monoclonal antibodies through cell fusion and hybridoma technology. Several types of monoclonal antibodies are outlined, along with their purification techniques and therapeutic applications in cancer treatment and other diseases. Gene therapy approaches including ex vivo and in vivo methods are briefly introduced.
This document summarizes monoclonal antibodies and gene therapy. It discusses the discovery of monoclonal antibodies by Kohler and Milstein in 1975. It describes the production process of monoclonal antibodies which involves immunizing mice, fusing spleen cells with myeloma cells to form hybridomas, and cloning cell lines. The document also discusses types of monoclonal antibodies including murine, chimeric, and humanized, as well as applications in cancer therapy, diagnostics, and immunosuppression. Gene therapy techniques like ex vivo and in vivo delivery are summarized along with strategies for cancer like suicide gene therapy using thymidine kinase.
monoclonal antibodies and engineered antibodiesMunawar Ali
This document provides an overview of monoclonal antibodies and engineered antibodies. It discusses the advantages and disadvantages of monoclonal versus polyclonal antibodies. Production methods like hybridoma technology and fermentation are described. Problems associated with monoclonal antibody therapy like HAMA response are covered. Applications in diagnosis, therapy and analytical uses are mentioned. Finally, the document discusses engineering antibodies by modifying regions to reduce immunogenicity and enhance functions.
Immunotherapeutic drugs can be broadly classified into four types: checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccines. However, immunotherapeutic drugs still have some problems, such as off-target side effects and poor pharmacokinetics.
Monoclonal antibodies are produced from single clones of B cells and bind to a specific epitope. Georges Köhler and Cesar Milstein developed hybridoma technology in 1975, which involves fusing B cells with myeloma cells to generate immortal hybridoma cell lines that secrete monoclonal antibodies. Hybridomas are selected by growing the cells in HAT medium, which kills unfused cells but allows hybridomas to survive and proliferate indefinitely. Monoclonal antibodies have numerous applications including cancer immunotherapy, diagnostic tests, and treatment of various diseases due to their high specificity and stability.
The document presents information on monoclonal antibodies. It discusses that monoclonal antibodies are identical antibodies produced through cell fusion techniques from a single parent cell. The summary includes that monoclonal antibodies have characteristics of homogeneity and specificity. The document also outlines the structure, advantages, disadvantages, production methods and applications of monoclonal antibodies such as in cancer treatment, immunosuppression, and autoimmune diseases. It concludes that monoclonal antibodies offer unique target specificity and can be engineered to reduce immunogenicity issues.
The document summarizes key concepts in immunology related to cancer and organ transplants. It discusses how the immune system can recognize and respond to tumors, mechanisms by which tumors evade immune detection, and approaches to cancer immunotherapy. It also covers immune mechanisms of graft rejection, types of transplants, and strategies to prevent rejection through immunosuppression.
This document discusses the use of monoclonal antibodies for cancer therapy. It provides background on conventional chemotherapy and highlights limitations. It then covers the history and development of monoclonal antibodies, including their production and mechanisms of targeting cancer cells through antigen cross-linking, activating death receptors, or delivering cytotoxic agents. Specific examples of toxin-immunoconjugates and antibody-directed enzyme prodrug therapy are described. The monoclonal antibody Rituximab is discussed as the first FDA-approved therapeutic monoclonal antibody for cancer.
This document discusses the use of monoclonal antibodies for cancer therapy. It provides background on conventional chemotherapy and highlights limitations. It then covers the history and development of monoclonal antibodies, including their production and mechanisms of targeting cancer cells, such as antigen cross-linking, activating death receptors, and delivering cytotoxic agents. Specific examples of toxin-immunoconjugates and antibody-directed enzyme prodrug therapy are described. The monoclonal antibody Rituximab is discussed as the first FDA-approved therapeutic monoclonal antibody for cancer.
The document discusses the pharmacokinetics of biotherapeutics, using rituximab as a case study. It covers absorption, distribution, elimination and accumulation of biotherapeutics. Rituximab is administered intravenously or subcutaneously. It has a long elimination half-life of 3 weeks and distribution is influenced by FcRn transport. Multiple doses may take up to 12 weeks to reach steady state. Analytical assays like LC-MS are discussed for quantifying biotherapeutics.
This document discusses types of immunity and immunomodulators. It describes active and passive immunity and the important components of the immune system. It then discusses immunomodulators that can suppress or enhance immune response, including immunosuppressants like corticosteroids and cyclophosphamide, and immunoenhancers like BCG vaccine, levamisole, and corynebacterium parvum. The document provides examples of immunomodulators and how they work to modulate the immune system.
The document discusses various aspects of the immune system and drugs that impact immunity. It describes the components of the immune system including lymphocytes, cellular and humoral immunity. There are two types of immunity: active and passive. Immunosuppressants discussed include corticosteroids, cyclophosphamide, azathioprine and methotrexate which act on different phases of the immune response. Immunostimulants covered are BCG vaccine, levamisole, corynebacterium parvum and tilorone which enhance the immune system.
Monoclonal antibodies drug targeting particuler carrier systemRoshan Lal Singh
monoclonal antibodies drug targeting particulate carrier system
presented by : - Roshan Lal Singh student of M.pharma 2nd semester University institute of pharmacy Pt. R. S. U. Raipur (C.G.).
Chemotherapy: Imperfect
Systematic nature of cytoxicity
Agents lack intrinsic anti-tumor selectivity
Anti-proliferative mechanism on cells in cycle, rather than specific toxicity directed towards particular cancer cell
Host toxicity: treatment discontinued at dose levels well below dose required to kill all viable tumor cells
cellular and molecular pharmacology - presentationSIMRAN VERMA
Immunotherapy involves boosting the body's natural defenses against cancer and certain infections. It works by stimulating or suppressing the immune system. Types of immunotherapy include monoclonal antibodies, fusion proteins, soluble cytokine receptors, recombinant cytokines, small molecule mimetics, and cellular therapies. Immunotherapy is used to treat cancer, infections, and allergies. It involves substances made by living organisms or in a laboratory that are administered through intravenous injection, orally, topically, or intravesically. Treatment length depends on the type of cancer and immunotherapy. Common side effects include flu-like symptoms, rashes, and gastrointestinal issues.
This document provides an overview of monoclonal antibodies (MAbs), including their definition, development, mechanisms of action, pharmacokinetics, adverse effects, and various therapeutic applications. Some key points discussed include:
- MAbs are antibodies produced from a single clone that are more uniform and abundant than natural antibodies. They can be produced in large quantities in the laboratory.
- Therapeutic uses of MAbs include immunosuppression for transplant rejection, treatment of autoimmune diseases by inhibiting cytokines like TNF-α, and various forms of cancer therapy by targeting cell surface antigens.
- Adverse effects are usually mild and related to cytokine release during infusion, but long-term suppression of physiological functions can also occur depending on
The renin-angiotensin system plays a key role in regulating blood pressure and fluid balance. Renin is synthesized in the kidneys and cleaves angiotensinogen to form angiotensin I, which is then cleaved by ACE to form angiotensin II. Angiotensin II increases blood pressure by constricting blood vessels and stimulating aldosterone release. It also acts in the kidneys, brain, and cells. The renin-angiotensin system is targeted by ACE inhibitors, angiotensin receptor blockers, and renin inhibitors to treat hypertension and related conditions. Substance P is a neurotransmitter involved in various physiological processes throughout the body.
Colchicum speciosum, commonly known as autumn crocus or meadow saffron, is a perennial herb native to Central Asia. It has pale purple flowers and a fleshy conical root. Parts of the plant including the seeds, leaves, and corm have been used medicinally. It contains colchicine and related compounds. Research has explored using derivatives of colchicine as potential anticancer agents due to their ability to arrest cell division, though clinical trials are still underway.
Hypersensitivity Type IV is a delayed type hypersensitivity that involves cell-mediated responses without antigen-antibody interactions. T lymphocytes recognize antigens that have been processed and presented by antigen-presenting cells via MHC molecules. Activated CD4+ T cells secrete cytokines that regulate the immune response, while activated CD8+ T cells kill cells displaying endogenous antigens on their MHC Class I molecules through the release of perforins and granzymes. This leads to loss of cell content and cell death.
Datura stramonium, commonly known as jimsonweed, is a poisonous plant native to North America. It grows as a weed worldwide in warm, temperate regions. The plant contains several tropane alkaloids, including atropine, hyoscyamine, and scopolamine. Historically, it has been used medicinally to treat conditions like asthma, pain, and motion sickness, and its active ingredients are still present in some modern drugs for treating gastrointestinal, respiratory, and eye conditions. The alkaloids can cause adverse effects if consumed, as the plant is poisonous.
Instrumentation of column and gas chromatographySadaqat Ali
This document provides an overview of column chromatography and gas chromatography instrumentation. Column chromatography separates components based on their differing rates of movement through a stationary phase packed in a column. Gas chromatography uses a mobile gas phase to carry vaporized sample components through a column coated with a liquid or solid stationary phase. Both techniques use instrumentation that includes columns, carrier gas systems, temperature control, sample injection ports, and detectors to separate and analyze sample components as they elute from the columns.
Local anesthetics and techniques of anesthesia Sadaqat Ali
This document provides information on local anesthetics including definitions, mechanisms of action, classifications, pharmacokinetics, clinical uses, and details on specific local anesthetics like lidocaine and dyclonine. It defines local anesthesia as loss of sensation in a body area without loss of consciousness. It discusses how local anesthetics work by inhibiting nerve membrane depolarization and action potential propagation. Common classes include esters, amides, and ketones. Clinical uses include analgesia, regional anesthesia, and treatment of arrhythmias or seizures.
Plasters are solid or semisolid masses that adhere to the skin when applied. They are used to provide protection and support, create an occlusive and macerating environment, and bring medication into close contact with the skin surface. They consist of a protective liner, drug-containing layer, and backing layer. Plasters are used for local or regional drug delivery and some therapeutic transdermal systems are used for long-term systemic delivery. Examples include nitroglycerin and estrogen patches.
Codeine is a commonly used antitussive (cough suppressant) that works by raising the stimulus threshold of the cough center in the brain. It is effective at reducing coughs by 40-60% compared to placebos. Codeine is also a mild opioid analgesic. Other antitussives include dextromethorphan (non-opioid), expectorants like guaifenesin to loosen mucus, and mucolytics like acetylcysteine that work to liquefy mucus in the respiratory tract.
A leader influences others through personal capabilities to achieve common goals. Key leadership qualities include knowledge, impartiality, experience, self-confidence and building confidence in others. To become a good leader, one should learn from experiences, express positive thoughts, and increase performance over time. Elements of leadership include developing a clear personality, being popular through hard work and sincerity, and having responsibilities like setting goals and informing members of changes. Islamic teachings emphasize the importance of choosing righteous leaders who establish Islamic values and impart justice.
The document provides guidance on self-assessment from various Islamic scholars and leaders. It advises that we should think carefully about our motives before acting and only do what pleases Allah. We are warned to control our desires and assess how close we are to Allah or Satan each moment, as the Prophet advised being wise by restraining desires and only acting for benefit after death. Umar also said to self-assess before the Day of Judgment so we can properly account for our actions.
Adrenergic blocking agents, also known as adrenergic antagonists, block alpha and/or beta receptor sites and have the opposite effect of adrenergic agents. They are classified based on the type of adrenergic receptor they block, including alpha1, alpha2, beta1, beta2, and beta3 receptors. Common uses include treatment of hypertension, heart failure, and benign prostatic hyperplasia. Side effects may include hypotension, tachycardia, and bronchospasm.
Elixirs are clear, sweetened alcoholic solutions intended for oral use. They contain 10-12% alcohol which helps dissolve ingredients. Elixirs differ from syrups in that alcohol is always present in elixirs and they remain clear while syrups can contain dyes. Common types of elixirs include simple non-medicated elixirs and medicated elixirs containing active ingredients. Elixirs are prepared by separately dissolving water and alcohol soluble components before combining the solutions and adding excipients like sweeteners, flavors, and preservatives.
This document discusses elixirs, including their definition as clear sweetened hydroalcoholic oral preparations containing 10-12% alcohol that are usually flavored. It outlines the differences between elixirs and syrups, the types of elixirs and their uses. Methods of preparation and common ingredients are provided, along with advantages like taste masking and examples like phenobarbital elixir. Potential adverse effects and proper storage are also mentioned.
हिंदी वर्णमाला पीपीटी, hindi alphabet PPT presentation, hindi varnamala PPT, Hindi Varnamala pdf, हिंदी स्वर, हिंदी व्यंजन, sikhiye hindi varnmala, dr. mulla adam ali, hindi language and literature, hindi alphabet with drawing, hindi alphabet pdf, hindi varnamala for childrens, hindi language, hindi varnamala practice for kids, https://www.drmullaadamali.com
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
-------------------------------------------------------------------------------
Find out more about ISO training and certification services
Training: ISO/IEC 27001 Information Security Management System - EN | PECB
ISO/IEC 42001 Artificial Intelligence Management System - EN | PECB
General Data Protection Regulation (GDPR) - Training Courses - EN | PECB
Webinars: https://pecb.com/webinars
Article: https://pecb.com/article
-------------------------------------------------------------------------------
For more information about PECB:
Website: https://pecb.com/
LinkedIn: https://www.linkedin.com/company/pecb/
Facebook: https://www.facebook.com/PECBInternational/
Slideshare: http://www.slideshare.net/PECBCERTIFICATION
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
2. Contents
Monoclonalantibody:
1- Definition
2- Introduction
3- Pharmacology
3.1) Mechanism of action of Mabs
3.2) Pharmacokinetics
4- Adverse effects
5- Therapeutic Potentials ofMAbs
5.1) Immunosupression - inhibition of alloimmune reactivity
5.2) Autoimmune diseases - inhibition of autoimmune reactivity
5.3)Cancer
5.4) Antiplatelet therapy
5.5) Infectious disease
5.6) Opthalmological disorders
5.7) Multiple sclerosis
5.8) Asthma
5.9) Juvenile diabetes
5.10) Systemic lupus erythematosus (SLE)
5.11) Active immunotherapy
5.12) in diagnostics
6- Brands available in market
7- references
3. Monoclonal antibody:
1- Definition
An antibody produced by a single clone of cells. A monoclonal antibody is therefore a
single pure type of antibody. Monoclonal antibodies can be made in large quantities in
the laboratory and are a cornerstone of immunology. Monoclonal antibodies are
increasingly coming into use as therapeutic agents.
2- Introduction
Antibody produced by a laboratory-grown cell clone, either of a hybridoma or a virus-
transformed lymphocyte, that is more abundant and uniform than natural antibody and
is able to bind specifically to a single site on almost any chosen antigen or reveal
previously unknown antigen sites: used as an analytic tool in scientific research and
medical diagnosis and potentially important in the treatment of certain diseases.
Abbreviation: MAb.
Monoclonal antibody production by somatic cell fusion or hybridoma technology was
introduced by Kolher and Milstein in 1975 (got Nobel Prize in 1984. Overall: The
technique involves fusing a normal antibody producing B cell with a myeloma cell to
produce a hybrid cell or hybridoma. The hybridoma would possess the immortal growth
properties of the myeloma cell while secreting the antibody produced by the B cell. The
resulting hybridoma could be cultured indefinitely thus providing large amounts of
homogeneous antibody for research purposes. The usefulness of monoclonal
antibodies stems from 3 characteristics
their specificity of binding
their homogeneity
Their ability to be produced in unlimited quantities.
4. 3- Pharmacology
3.1) Mechanism of action of MAb’s
The mechanism by which MAbs achieve therapeutic effect is not very clear. Potential
mechanisms include:
Blocking or steric hindrance of the function of target antigen i.e., T-lymphocytes,
B lymphocytes, tumour necrosis factor-a (TNFa) and interleukin (IL) which are
capable of transducing intracellular signals.
Cytotoxicity to the cell expressing target AG by ADCC or CDC.
Inhibition of growth factors: Epidermal growth factor receptor (EGFR) is a cell
surface receptor involved in regulation of cell proliferation and survival. Also new
vessels grow to feed the cancer cells through this factor. These factors can be
inhibited to arrest growth of cancer cells e.g., cetuximab act as EGFR inhibitor.
3.2) Pharmacokinetics
MAbs are used by intravascular route and remain essentially intravascular.
Intravenous injection is not always be appropriate for long-term treatment for a
variety of reasons. Hour-long infusions require a hospital environment and are
often associated with mild to very severe side effects. Continuous and sustained
delivery of antibodies can lead to induction of neutralizing anti-idiotypic immune
responses, which sometimes develop when massive doses of purified
immunoglobulins are repeatedly injected into patients. Additionally, the
bioavailability of therapeutic antibodies is often detrimental to the treatment
efficacy. They have small volume of distribution and limited tissue penetration.
They remain in circulation for 2 days to 2 weeks. Another limitation is the high
cost of recombinant proteins certified for human use.
5. Antibodies can have exquisite specificity of target recognition and thus generate
highly selective outcomes following their systemic administration. While
antibodies can have high specificity, the doses required to treat patients,
particularly for a chronic condition, are typically large. Fortunately, advances in
production and purification capacities have allowed for the exceptionally large
amounts of highly purified MAbs to be produced. Additionally, genetic
engineering of antibodies has provided a stable of antibody-like proteins that can
be easier to prepare.
Genetic manipulations of the immunoglobulin molecules are effective means of
altering stability, functional affinity, pharmacokinetics, and biodistribution of the
antibodies required for the generation of the 'magic bullet.
4- Adverse effects
Adverse effects with MAbs are related to one of three mechanisms:
Xenogenetic nature of MAb used
Suppression of physiological function
Activation of inflammatory cells or mediators after binding of MAb to its
target
6. Adverse effects with naked MAbs are usually mild and often related to an 'allergic'
reaction and occur while the drug is being first infused. This reaction is attributed to
massive cytokine release resulting from transient activation of T
lymphocytes. Reactions may include fever, chills, weakness, headache, nausea,
vomiting, diarrhea, low blood pressure, and rashes. Some MAbs cause leucopenia,
thrombocytopenia, and anemia. Conjugated MAbs cause more side effects and the
actual effects depend to which substance it is attached. Sometimes it also causes
suppression of physiological function depending on specificity of tissue targets. Thus
anti-lymphocytes MAb cause immunosupression. There is also an increased risk of
infection and cancer development. AntiTNF-a MAb treatment has been reported to
increase the reactivation of tuberculosis because it interferes with the cellular response
against mycobacteria and this adverse effect is more in areas with high incidence of
tuberculosis. AntiTNF-a MAb treatment also leads to development of
lymphomas. Rituximab may lead to depletion of plasma cells and cause
hypogammaglobulinemia due to its action on B-cells.
5- Therapeutic Potentials of MAbs
MAbs were being used in laboratory research and in medical tests since the mid 1970s,
but their effectiveness in disease treatment was limited. MAbs created much excitement
in the medical world and in the financial world in 1980s especially as a potential cure for
cancer. Although this resulted in great optimism that a therapeutic 'magic bullet' could
be engineered, success with MAbs was many years away. By early 21st century,
several drugs based on MAbs were introduced for a wide variety of therapeutic uses.
Herceptin, a humanized MAb for breast cancer treatment, became the first drug
designed by biomolecular engineering approach to be approved by the FDA. A recent
survey suggested that ¼ of all biotech drugs in development are MAb based. At least an
additional 400 MAbs are under clinical trials to treat cancer, transplant rejection or to
combat autoimmune or infectious diseases. It is now possible to obtain engineered
antibodies, chimeric, or humanized or fully human MAbs via the use of phage display
technology or of transgenic mice. Important therapeutic implications of MAbs are given
in the preceding chapter.
5.1) Immunosupression - inhibition of alloimmune reactivity
In 1985, Muromonab CD-3 (OKT3) a murine MAb, was the first to be approved by the
US FDA for clinical use in humans, for prevention of graft rejection in renal transplant
patient. As first line or in steroid resistance rejection therapy, OTK3 has proved
efficacious and improved graft survival. It specifically reacts with the T-cell receptor-CD3
complex on the surface of circulating human T cells. OKT3 binds to a glycoprotein (the
20-kd epsilon chain) on the CD3 complex to activate circulating T cells, resulting in
7. transient activation of T cells, release of cytokines and blocking of T-cell proliferation
and differentiation. Nearly all functional T cells are transiently eliminated from the
peripheral circulation. Although T cells reappear in the circulation during the course of
treatment, these cells are CD3-negative and are not capable of T-cell activation.
However, the use of OKT-3 was hampered due to production of Ags and rapid
clearance from circulation. This led to development of humanized OKT-3 which is under
investigation.
Acute graft rejection is a T-cell mediated immune response and depends on presence
of IL-2. IL-2 binds to IL-2 receptor. In the search for more specific immunosupression
with MAb L- 2 Receptor (IL-2R), that is expressed on T-cells, which were chosen as
target. Chimeric and humanized MAbs, basiliximab, and daclizumab were developed to
bind to IL-2R. They competitively antagonized IL-2 or caused elimination of activated T-
cells. They have been efficacious in preventing acute rejection episode after renal
transplant.
5.2) Autoimmune diseases - inhibition of autoimmune reactivity
For the treatment of autoimmune disease, MAbs need to target immune response cells,
i.e., B or T-cells. MAb may function as an immunosuppressant by removing activated
cells, blocking their function or normalizing elevated levels of proinflammatory cytokine.
Therapeutic targets in this condition include T-cell surface Ags, T-cells activation Ags,
molecules involved in T/B cell interaction, adhesion molecules, and cytokines.
The most promising result emerged from TNF-a blocking therapy in rheumatoid arthritis
(RA) and Crohn's disease. TNF is a cytokine produced by activated monocytes and
macrophages. The cytokine is actively produced at the synovial and mucosal sites of
inflammation in RA and Crohn's disease. It is involved in vasodilation, increased
vascular permeability, and activation of platelets and regulation of production of acute
phase proteins involved in inflammation. TNF is also actively produced in various
infectious diseases such as sepsis, malaria, adult respiratory disease syndrome, and
AIDS.
TNF is considered to have an important role in autoimmune inflammatory disease. This
led to the discovery of infliximab which is a chimeric MAb and found to be effective in
various animal models and clinical trial for RA and Crohn's disease. It is clinically
beneficial in Crohn's disease, reduces the response duration and also reduces fistula
formation. The first trail of usefulness of infliximab in RA was shown in 1994. Infliximab
halts radiographic progression of RA and also clinically cures the disease. Adalimumab,
a humanized IgG1 MAb is also approved for the treatment of RA. It binds to soluble and
8. cell membrane-bound TNF-a. It is proved to be efficacious and halts radiological
progression of the disease. Anti TNF-a MAb treatment has shown promise in patients
with seronegative spondyloarthropathies and psoriatic arthritis. Anti-IL-6 and anti-IL-6
receptor MAbs have also been found to be useful in RA as IL-6 is elevated in patients
with RA and levels of RA correlates with disease activity and extent of joint erosion.
5.3)Cancer
Classical therapeutic modalities such as surgery, radiation, and chemotherapy not only
fail to cure the great majority of malignant tumors, but also their employment often leads
to severe and debilitating side effects. Immunotherapy as a fourth modality of cancer
therapy has already been developed and proven to be quite effective. Strategies for the
employment of antibodies for anti-cancer immunotherapy include:
(1) Immune reaction directed destruction of cancer cell
(2) Interference with the growth and differentiation of malignant cells
(3) Antigen epitope directed transport of anti-cancer agents to malignant cells
(4) anti-idiotype vaccines
(5) Development of engineered (humanized) mouse monoclonals for anti-cancer
therapy.
In addition, a variety of different agents (e.g., toxins, radionuclides, chemotherapeutic
drugs etc.) have been conjugated to mouse and human MAbs for selective delivery to
cancer cells.
Unconjugated antibodies show significant efficacy in the treatment of breast cancer,
non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Promising new targets for
unconjugated antibody therapy include cellular growth factor receptors, receptors, or
mediators of tumor-driven angiogenesis and B cell surface antigens other than CD20.
One immunoconjugate containing an antibody and a chemotherapy agent exhibits
clinically meaningful anti-tumor activity in acute myeloid leukemia. Clinical trials of MAb
therapy are in progress for almost every type of cancer. Rituximab was the first MAb
used for treatment of cancer. It is chimeric IgG-1 MAb directed against CD20, which is a
transmembrane protein on mature B-lymphocytes. Its efficacy has been demonstrated
against low grade and follicular non-Hodgkin's lymphoma relapse. Rituximab has also
been useful in Waldenstrom's macroglobulinemia, posttransplantation lymphoma, and
multiple myeloma. CD52 MAb (Campath-1H) has also been studied to lyse malignant
hemopoetic cells. CD52 MAb provides an effective therapy for chronic leukemia of T-
cell or B-cell origin that is resistant to conventional chemotherapy. Anti-tumor therapy
with MAbs targets growth factor receptor too.
9. 5.4) Antiplatelet therapy
Acute coronary syndromes and percutneous coronary intervention share a common
physiological mechanism of intimal disruption and platelet aggregation. Glycoprotein
IIb/IIIa receptor antagonist which interrupt the final common pathway of platelet
activation and aggregation are used for acute therapy. Abciximab was the first
antagonist to be evaluated. It inhibits the clumping of platelets by binding to surface
receptors that normally are linked by fibrinogen. It is helpful in preventing the reclogging
of the coronary arteries.
5.5) Infectious disease
Palivizumab, a humanized MAb directed against Respiratory Syncytial virus is used for
the treatment of premature infants and infants with bronchopulmonary dysplasia A MAb
was also found to be useful to cure West Nile fever in mice.
5.6) Opthalmological disorders
Daclizumab has shown to be efficacious for noninfectious uveitis. Ranibizumab
(Lucentis) is a recombinant humanized IgG1 kappa isotype monoclonal antibody
fragment designed for intraocular use, which competitively binds and inhibits VEGF.
Therefore, indicated for the treatment of neovascular (wet) age related macular
degeneration.
5.7) Multiple sclerosis
Natalizumab, a humanized MAb was approved by FDA in November, 2004 for relapsing
form of multiple sclerosis, but was withdrawn in February 2005 after three patients in the
drug's developed progressive multifocal leukoencephalopathy (PML) during clinical
trial. On 24th March, 2006 the FDA lifted the hold on clinical trials of natalizumab after
confirming that there were no additional PML cases. In March, 2006, FDA consulted its
advisory committee on drugs for peripheral and central nervous systems about the
possibility of making natalizumab available to appropriate MS patients. The committee
recommended a risk-minimization program with mandatory patient registration and
periodic follow-up.
5.8) Asthma
Omalizumab MAb has shown promise in allergic asthma. It acts by binding to IgE thus
preventing IgE from binding to mast cells. Omalizumab has shown to reduce serum IgE
levels, reduce inhaled steroid consumption and was also well tolerated by children and
adults.
10. 5.9) Juvenile diabetes
Anti-CD3 MAb is in phase II trial for type I juvenile DM. This MAb targets an antigen
expressed on T lymphocytes that is responsible for destruction of islet cells of pancreas
and thus could slow the disease progression.
5.10) Systemic lupus erythematosus (SLE)
IL-6 levels are elevated in human and murine SLE. Blocking the action of IL-6
ameliorates disease activity in murine model of SLE. A humanized MAb is in Phase I of
clinical trial. T cells, B cells and monocytes from patients with SLE expressess CD40 L
on their surface which have been found to produce autoantibodies in vitro. Therefore,
humanized anti-CD40L IDEC-131 was tried for SLE but not found to be successful.
Another humanized anti-CD40L Mab, ruplizumab was effective in SLE, but increased
the incidence of myocardial infarction. Therefore the trials were discontinued.
Rituximab has also been shown to be effective in patients of SLE with
glomerulonephritis, by causing B-cell depletion. B-cells in SLE display abnormal
signaling, express aberrant cell surface markers and finally produce autoantibody and
present auto antigen to T cells at increased rates.
5.11) Active immunotherapy
Direct evidence of the importance of gangliosides as potential targets for active
immunotherapy has been suggested by the observation that human MAbs against these
glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the
cellular over-expression and shedding of gangliosides into the interstitial space may
play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis,
thereby representing a new target for anticancer therapy.
5.12) in diagnostics
Generally, MAbs are being used as invaluable reagents in diagnostics. In fact, they
have played a major role in deciphering the functions of various bio-molecules in cryptic
biosynthetic pathways. These have also become the reagents of choice for identification
and characterization of tumor specific antigens and have become a valuable tool in the
classification of cancer.
11. 6- Brands available in market
Name Brandname Uses
Abciximab ReoPro Inj: 2 mg/ml, platelet aggregation inhibitor
Adalimumab Humira 40 mg per 0.8 mL Rheumatoid arthritis, Crohn's
Disease,
Plaque Psoriasis, Psoriatic
Arthritis, Ankylosing
Spondylitis, Juvenile
Idiopathic Arthritis,Hemolytic
disease of the newborn
Alemtuzumab Campath, MabCampath
injectable IV solution
10mg/mL
Multiple sclerosis
Altumomab pentetate Hybri-ceaker 10 mL colorectal cancer (diagnosis)
Arcitumomab CEA-Scan gastrointestinal cancers
(diagnosis)
Daclizumab ZENAPAX Inj-IV:40 mg/ml indicated in conditions
like Metastatic.
7. References
www.druginfosys.com
12. www.aafp.org
www.bio.tamu.edu
Monoclonal antibodies: Pharmacological relevance by Jasleen Kaur, DK
Badyal, PP Khosla Department of Pharmacology, Christian Medical College and Hospital, Ludhiana, India