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.
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
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
Immunotherapy, a type of cancer treatment designed to eradicate disseminated cancer by harnessing the potential of the immune system. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system -this can be achieved through various approaches that utilize adaptive or innate immunity. The main types of immunotherapy can be broadly subdivided into non-antigen-specific and antigen-specific categories. Non-antigen-specific strategies include nonspecific immune stimulation and Immune checkpoint inhibitors, whereas antigen-specific strategies include adoptive cell transfer of autologous cancer-specific T cells and various therapeutic vaccination approaches.
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.
Immunotherapy, a type of cancer treatment designed to eradicate disseminated cancer by harnessing the potential of the immune system. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system -this can be achieved through various approaches that utilize adaptive or innate immunity. The main types of immunotherapy can be broadly subdivided into non-antigen-specific and antigen-specific categories. Non-antigen-specific strategies include nonspecific immune stimulation and Immune checkpoint inhibitors, whereas antigen-specific strategies include adoptive cell transfer of autologous cancer-specific T cells and various therapeutic vaccination approaches.
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.
Diploma nursing Extension student International institute of health science jinja,Uganda presenting the Antineoplastic drugs, the main objectives is
1.definition.
2.classes of Antineoplastic drugs.
3.Different types of drugs in each class.
4Different forms,dosage,indication,Adverse effects of some common Antineoplastic.
Nursing interventions in Antineoplastic drugs.
a short presentation about the types of treatments used in cancer therapy, including traditional chemotherapy, targeted therapy, immunotherapy and hormonal therapy. also a short talk about side effects and administration of the CTX drugs.
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
Monoclonal Antibodies and it's applications.pptxAfroj Shaikh
SlideShare Description: Monoclonal Antibodies and Their Applications
In the rapidly advancing field of biotechnology, monoclonal antibodies have emerged as powerful tools with diverse applications. This SlideShare presentation provides a comprehensive overview of monoclonal antibodies and their wide-ranging uses in various fields, including medicine, research, and diagnostics.
The presentation begins by explaining the fundamental concept of monoclonal antibodies, highlighting their unique structure and production process. It delves into the significance of hybridoma technology, which allows for the generation of large quantities of identical antibodies derived from a single parental cell line.
Moving on, the SlideShare explores the applications of monoclonal antibodies in the field of medicine. It elucidates how these antibodies are employed in targeted therapies, such as cancer immunotherapy. The presentation highlights the remarkable specificity of monoclonal antibodies in recognizing and binding to specific targets, thereby enabling precise and tailored treatment approaches. It also discusses the role of monoclonal antibodies in autoimmune diseases, infectious diseases, and organ transplantation.
Furthermore, the presentation sheds light on the use of monoclonal antibodies in research and diagnostics. It explains how these antibodies are utilized as indispensable tools in laboratory research, facilitating the identification and characterization of various biomarkers and molecules. It also showcases their utility in techniques such as enzyme-linked immunosorbent assays (ELISA), flow cytometry, and immunohistochemistry.
The SlideShare emphasizes the impact of monoclonal antibodies on the development of novel therapeutic modalities, including antibody-drug conjugates and bispecific antibodies. It touches upon the challenges and future prospects in the field, highlighting ongoing research efforts and advancements in antibody engineering.
With visually appealing slides, concise and informative content, this SlideShare presentation on monoclonal antibodies provides a valuable resource for scientists, healthcare professionals, students, and anyone interested in understanding the significance and applications of these remarkable biotechnological innovations.
2. Conventional Anti-Cancer Therapy
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
2
3. History
Emil von Behring in 1890
Discovered antibodies
Paul Ehrlich (16 years later)
Coined phrase, “magic bullets and poisoned arrows”
Kohler and Milstein in 1975
Discovery of monoclonal antibodies (mAb) directed
against well-characterized antigens
3
4. Rationale
Mab as efficient carriers for delivery of anti-tumor agents
Enhanced vascular permeability of circulating
macromolecules for tumor tissue.
Normal tissue: blood vessels have intact endothelial
layer
Tumor tissue: blood vessels leaky and so small
Tumor tissue generally do not have a lymphatic drainage
4
system.
5. Production of monoclonal antibodies
Biotech Resources. 1989. Monoclonal antibody technology -- the basics.
5
6. Patho-physiology of Tumor Tissue
Angiogenesis
Hyper vasculature
Impaired lymphatic drainage
***Due to these characteristics, tumors can be exploited for
tumor-selective drug delivery
6
8. 3 mechanisms resulting in apoptosis
Antigen cross-linking
Activation of death receptors
Blockade of ligand-receptor growth or survival pathways
8
9. 1. Antigen cross-linking
Target growth factor receptor
Antagonize ligand-receptor signaling
Growth-factor signaling mediated by the receptor
tyrosine kinase is inhibited
EGFR (epidermal growth factor receptor)
FGFR (fibroblast growth factor receptor)
VEGFR (vascular endothelial growth factor)
Results in arrest of tumor cell growth
9
10. 2. Activation of death receptors
Death receptors : members of TNF receptors family.
Cross-link targeted surface antigens on tumor cells and
antibody agonists that mimic ligand-mediated activation
of specific receptors
Response: intracellular Ca II ions increase
Activate caspase-3 and caspase-9 (involved in cell
apoptosis)
10
12. 3. Delivery of cytotoxic agents
Physically link antibodies to toxic substances for delivery
Radio-immunoconjugates (aim of delivering radiation
directly to the tumor)
Toxin-immunoconjugates (deliver toxins intracellularly)
Antibody-directed enzyme pro-drug therapy (ADEPT):
localize enzymes to tumor cell surfaces
12
13. General drug delivery system
Drug molecules bound to
macromolecule through spacer
molecule
Drug released from
macromolecule after cellular
uptake of the conjugate
Targeting moiety =
monoclonal antibody
13
14. Toxin immunoconjugates
3 methods to attach cytotoxic drug to variable regions of
mAb
a. Couple drug to lysine moieties in the mAb
b. Generation of aldehyde groups by oxidizing the
carbohydrate region and subsequent reaction with amino-
containing drugs or drug derivatives
c. Couple drugs to sulfhydryl groups by selectively
reducing the interchain disulfides near the Fc region of
14 the mAb
15. Immunoconjugate
BR96-doxorubicin conjugate (BR96-DOX)
Promising toxin-immunoconjugate
mouse/human chimeric mAb
Targets antigen over-expressed on surface of human
carcinoma cells of breast, colon, lung, and ovary
Disulfide reduction attaches mAb to drug, BR96
Dose that can be safely administered every 3 weeks is
insufficient
15
17. Other examples of toxin-
immunoconjugates
KS1/4-MTX
Conjugate of methotrexate (MTX)
Coupling of MTX to the lysine moieties of the mAb
KS1/4-DAVLB
Conjugate of vinca alkaloid derivatives
Vinca alkaloid derivatives attached to amino groups of
lysine residues on KS1/4 mAb
17
18. Why are these toxin-immunoconjugates
unsuccessful?
Cause gastrointestinal toxicity
Inner regions of solid tumors poorly vascularized and have
low blood flow (reduce amount of immunoconjugate
reaching these parts of the tumor)
Antigen expression is heterogenous on tumor cells
Restricts the amount of cells that can be effectively
targeted by antibody conjugates
18
19. ADEPT ENZYMES (Antibody-
directed enzyme pro-drug therapy)
Chemically link the mAb to the enzyme of interest; can
also be a fusion protein produced recombinantly with the
antibody variable region genes and the gene coding the
enzyme
Convert subsequently administered anti-cancer pro-drugs
into active anti-tumor agents
Upon binding to targeted enzymes, it is converted into
active drug
19
21. Anti-growth factor mAb Therapy
Angiogenesis
Formation of nascent blood vessels
VEGF
Protect endothelial cells from apoptosis
Activity mediated by tyrosine kinase receptors, VEGFR
1 and VEGFR 2
Functions indirectly as survival factor for tumor cells
Inhibit VEGF signaling
Block the receptor
Inhibits tumor growth and metastasis
Deprives tumors of nutrient-providing blood vessels
21
22. RITUXIMAB (rituxan)
1st therapeutic mAb approved by FDA in 1997
CD20 antigen function: cell cycle progression
Binding Rituximab to CD-20 causes: autophosphorylation,
activation of serine/tyrosine protein kinases -- induces
apoptosis
Response rates of 50% to 70% in follicular lymphomas
Response rates of 90% to 100% when used in combination
with various chemotherpay procedures
22
24. Toxic effects of Rituximab
Short-lived mild reactions to infusion after first
treatment:
fever
chills
rashes and nausea
24
25. FDA-approved monoclonal antibodies for cancer treatment
Name of drug Type of cancer it treats
Alemtuzumab (Campath) Chronic lymphocytic leukemia
Brain cancer
Colon cancer
Bevacizumab (Avastin)
Kidney cancer
Lung cancer
Colon cancer
Cetuximab (Erbitux)
Head and neck cancers
Source: Food and Drug Administration (FDA), Center for Drug Evaluation and Research
25
26. Estimated New Cancer Cases and Deaths Worldwide for Leading Cancer Sites by Level of
Economic Development, 2008. Source: GLOBOCAN
26
27. CONCLUSION
Researchers hope to define the optimal combinations of the
use of mAb with conventional chemotherapeutic agents and
with radiation therapy
Determine best therapy candidates and expand clinical
trials to other tumor types.
27