This document discusses various types of immunotherapy used to treat diseases like cancer. It describes active immunotherapy which aims to stimulate the immune system, such as cancer vaccines, and passive immunotherapy which introduces immune system components from outside the body like monoclonal antibodies. The document also covers humanized antibody therapy, where mouse or rat antibodies are combined with human antibodies to make them less likely to trigger an immune response. Methods used to humanize antibodies include grafting complementarity determining regions and hybridoma technology using transgenic mice.
This slideshare conatins detailed overview of immunotheraphy,humanisation of antibodies and its clinical application
this is the topic from cellular and molecular pharmacology of m pharmacy first year
immunotheraphy is further classified to its various types which has been discussed individually
its also conatins various immunotheraphy drugs which has other clinical advantages
This slideshare conatins detailed overview of immunotheraphy,humanisation of antibodies and its clinical application
this is the topic from cellular and molecular pharmacology of m pharmacy first year
immunotheraphy is further classified to its various types which has been discussed individually
its also conatins various immunotheraphy drugs which has other clinical advantages
Screening methods of immunomodulators by shivam diwakerShivam Diwaker
Immune Modulators are the substances or drugs or chemical compounds that are used for the modification in the Immune system such as stimulate and suppress.
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
Introduction to Immunotherapeutics
Cell mediated & humoral immunity, Immunosuppressants, Immunostimulants
Presented by
G. Sai Swetha
Department of Pharmacology
In vivo is the Latin word which means with in the living body.
When effects of various biological entities are tested on whole, living organism or cells, usually animals including humans and plants.
Animal testing and clinical trials are major elements of in-vivo research.
In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject in drug discovery.
example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug.
Harry Smith found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not.
In microbiology Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro.
In vitro studies within the glass, i.e., in a laboratory environment using test tubes, petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease.
In vitro toxicology:-
The bridge exists between new drug discovery and drug development.-
Provide information on mechanism of action of a drug
Provides an early indication of the potential for some kinds of toxic effects, allowing a decision to terminate or to proceed further.
In vitro methods are widely used for:-
Screening and ranking chemicals
Get a platform for animal studies for physiological actions
Studying cell, tissue, or target specific effects
Improve subsequent study design
Advantages and Disadvantages:-
Faster than in vivo studies
Less expensive to run
Less predictive of toxicity in intact organisms
In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.
The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests.
Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo.
Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method.
Two solutions are now commonly accepted:
Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems).
Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model.
The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods.
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
Screening methods of immunomodulators by shivam diwakerShivam Diwaker
Immune Modulators are the substances or drugs or chemical compounds that are used for the modification in the Immune system such as stimulate and suppress.
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
Introduction to Immunotherapeutics
Cell mediated & humoral immunity, Immunosuppressants, Immunostimulants
Presented by
G. Sai Swetha
Department of Pharmacology
In vivo is the Latin word which means with in the living body.
When effects of various biological entities are tested on whole, living organism or cells, usually animals including humans and plants.
Animal testing and clinical trials are major elements of in-vivo research.
In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject in drug discovery.
example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug.
Harry Smith found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not.
In microbiology Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro.
In vitro studies within the glass, i.e., in a laboratory environment using test tubes, petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease.
In vitro toxicology:-
The bridge exists between new drug discovery and drug development.-
Provide information on mechanism of action of a drug
Provides an early indication of the potential for some kinds of toxic effects, allowing a decision to terminate or to proceed further.
In vitro methods are widely used for:-
Screening and ranking chemicals
Get a platform for animal studies for physiological actions
Studying cell, tissue, or target specific effects
Improve subsequent study design
Advantages and Disadvantages:-
Faster than in vivo studies
Less expensive to run
Less predictive of toxicity in intact organisms
In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.
The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests.
Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo.
Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method.
Two solutions are now commonly accepted:
Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems).
Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model.
The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods.
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
immuno therapy is the treatment modality used to treat, cure the cancer, and kill the cancer tumor by increasing the self defense system to fight against cancer cell
Immunotherapeutics (Types of immunotherapeutics, humanisation antibody therap...NikitaBankoti2
Immunotherapy
➢ Treatment to stimulate or restore the ability of the immune (defence) system to fight
against infection or disease.
➢ It is also sometimes called Biologic therapy or Biotherapy.
➢ Biological therapy is thus any form of treatment that uses the body’s natural abilities
that constitute the immune system to fight infection and disease or to protect the body
from some of the side effects of treatment e.g. – cancer.
Types of Immunotherapeutics
1. Monoclonal antibody
2. Cancer vaccines therapy
3. Immune checkpoint inhibitors
4. Non-specific Immunotherapies
5. Chimeric antigen receptor (CAR) T-cell therapy
Humanized Antibody- They are antibodies from non-human species whose protein sequences have
been modified to increase their similarity to antibody variants produced naturally in humans.
➢The process of humanization is usually applied to monoclonal antibodies developed for administration
to humans. (e.g- antibodies developed as anti-cancer drugs)
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
We all have good and bad thoughts from time to time and situation to situation. We are bombarded daily with spiraling thoughts(both negative and positive) creating all-consuming feel , making us difficult to manage with associated suffering. Good thoughts are like our Mob Signal (Positive thought) amidst noise(negative thought) in the atmosphere. Negative thoughts like noise outweigh positive thoughts. These thoughts often create unwanted confusion, trouble, stress and frustration in our mind as well as chaos in our physical world. Negative thoughts are also known as “distorted thinking”.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
2. CONTAIN
IMMUNOTHERAPY
TYPES OF IMMUNOTHERAPY
HUMANIZATION ANTIBODY THERAPY
METHODS OF HUMANIZATION OF ANTIBODIES
IMMUNOTHERAPEUTIC IN CLINICAL PRACTICE
3. IMMUNOTHERAPY
• Immunotherapy is the treatment of disease by activating or suppressing the immune system.
• Immunotherapies designed to elicit or amplify an immune responses are classified as
activation immunotherapies, while immunotherapies that reduce or suppress are classified as
suppression immunotherapies.
• Immunotherapy also called as Biologic therapy is a type of cancer treatment that boosts the
body natural defenses to fight cancer. Immunotherapy may work by Stopping or slowing the
growth of cancer cells. Stopping cancer from spreading to other parts of the body.
4. How it works?
• Immunotherapy includes a wide variety of treatments
that work in different ways:
• By boosting the body's immune system in a very general
way.
• Helps to train the immune system to attack cancer cells
specifically,
• Giving immune system components, such as man-made
immune system proteins.
6. Active Immunotherapy
• It is the type of immunotherapy that attempts to stimulate the
host’s intrinsic immune response to a disease. Further divided into:
• Specific active immunotherapy
• Non specific active immunotherapy
Specific active immunotherapy The generation of cell mediated and
antibody immune responses focused on specific antigen.
E.g. cancer vaccines , cellular therapies, adjuvants
7. • Cancer vaccines: cancer vaccines may contain cancer cells part of the
cell, or purified tumor specific antigen.
• Two categories of cancer vaccine are:
• Cell based in which the patient cancer cell is cultured with patients own
immune system cells and derived back to the same patient.
• Vector based in which the engineered virus or other vector is used to
introduce cancer specific proteins and other molecule in order to
stimulate the patient immune system to recognize the tumor cells to
fight the cancer.
• Cellular therapies: These are single type agent derived from the cancer
patients which are modified in the lab, to become more adapt at
recognizing and killing the tumor cells. This type of immunotherapy is
designed to boost specific part of immune system to cause tumor cell
death Eg lymphocyte activated killer cell therapy.
• Adjuvant immunotherapy: an adjuvant is an any material which when
injected together with an antigenic protein or other substance like
monoclonal antibodies, cancer vaccines increases or boost the immune
response to the particular system. Eg BCG vaccine
8. Non specific immunotherapy: don't target cancer cells specifically,
generation of general immune system response.
• Cytokines are chemicals made by some immune system cells.
They are crucial in controlling the growth and activity of other
immune system cells and blood cells in the body.
• Cytokines destruct tumour cell by two mechanism:
• direct antitumor e.g. TNF alpha,IL-6
• Indirect enhancement of antitumor Eg. IL12 response promote T-
cell and NK cell growth.
9. Passive Immunotherapy
• Passive immunotherapy This comprised of antibodies and other immune system
component that are made outside the body and administered to the patient to
provide immunity against the disease.
• It do not stimulate a patient immune system to actively respond to a disease in the
way vaccines does.
• Adoptive Cell Therapy
• Immunomodulators
• Targeted Antibodies
• Oncolytic Virus Therapy
10. • 1. Adoptive Cell Therapy: Adoptive cell therapies use immune cells to fight cancer.
There are two main approaches:
• Immune cells are isolated, expanded, and reintroduced into the cancer patient
• Immune cells are genetically modified to "boost" their cancer-fighting ability, and then
reintroduced into the cancer patient.
• Eg Chimeric Antigen Receptor (CAR) T-cell Therapy (Modified Cells)
• 2. Immunomodulators : Immunomodulators regulate or "modulate" the activity of the
immune system.
• Immunomodulators can be loosely separated into four groups;
• checkpoint inhibitors-checkpoint inhibitors can reduce immune suppressive
mechanisms - increasing the immune system's response to cancer and promoting the
elimination of cancerous cells.
• Cytokines (These molecular "messengers" enable immune cells to communicate and
mount a coordinated response to a target antigen, the first to be approved was a
cytokine called interferon-alpha 2 (IFN-22) back in 1986).
• Drugs: Immunostimulants (Levamisole, thalidomide, BCG, Interferons,)
Immunosuppressant (Cyclosporine, Tacrolimus, glucocorticoid, Cytotoxic drugs etc.)
• Adjuvants
11. • 3. Monoclonal antibodies :Many copies of a specific
Antibody can be made in the lab These are known as
Monoclonal Antibodies (mAbs or moAbs).
• These Antibodies can be useful in fighting diseases
because they can designed specifically to only target a
certain antigen, such as one that is found on cancer cells.
• Over the past 15years, the US FDA has approved about a
mAbs to treat certain cancers.
• Two types of monoclonal antibodies are used in cancer
treatment:
• 1) Naked mAbs are antibodies that work by themselves.
• 2) Conjugated mAbs are those joined to a chemotherapy
drug, radioactive particles, or a toxin.
12. • 4. Oncolytic Virus Therapy: Viruses are infectious agents
that are capable of infecting living cells, hijacking their
genetic machinery, which allows the viruses to replicate
inside of them.
• Modified versions of viruses can be created to target and
attack cancer cells. These are termed "oncolytic viruses" as
they are designed to target cancer specifically.
• The viruses can be engineered to decrease their ability to
infect "normal" cells and they can also be used as delivery
vehicles, transporting therapeutic payloads to cancer cells.
• The first oncolytic virus therapy was approved by the FDA in
2015-T-VEC for treatment of melanoma.
14. What are antibodies?
• An antibody is a protein used by the immune
system to identify and neutralize foreign objects
like bacteria and viruses. Each antibody
recognizes a specific antigen unique to its target.
• Monoclonal antibodies (mAbs) are antibodies that
are identical because they were produced by one
type of immune cell.
• Polyclonal antibodies are antibodies that are
derived from different cell lines..
15. Humanized antibody
• A type of antibody made in the laboratory by combining a human antibody
with a small part of a mouse or rat monoclonal antibody. The mouse or rat
part of the antibody binds to the target antigen, and the human part makes
it less likely to be destroyed by the body's immune system.
• The process of "humanization" is usually applied to monoclonal antibodies
developed for administration to humans (for example, antibodies developed
as anti-cancer drug).
16. Why humanization is necessary ?
• Humanization can be necessary when the process of developing a specific
antibody involves generation in a non-human immune system (such as
that in mice).
• The protein sequences of antibodies produced in this way are partially
distinct from homologous antibodies occurring naturally in humans, and
are therefore potentially immunogenic when administered to human
patients.
17. Methods of humanization of
antibodies
• Humanized antibodies are produced by:
i. Grafting complementarity determining regions (CDRs)
ii. Memory B cell immortalization
iii. Hybridoma technology using transgenic mouse
iv. Hybrid-hybridoma
v. Human antibody display
vi. Recombinant antibodies by cloning v-region genes
18. Grafting complementarity determining
regions (CDRs)
Complementarity-determining regions (CDRs) of murine Antibody (variable regions)
Grafted into variable regions of human antibody
which were then joined to constant regions of human antibody
Reshaped (humanized) antibody
19.
20.
21. Hybridoma technology using
transgenic mouse
• This technology is a slightly modified version of traditional hybridoma technology,
Here, the hybridoma is produced from the spleen cells of transgenic mice in which
the immunoglobulin genes are knocked out and replaced with human
counterparts. This is followed by the antigen immunization.
• The steps thereafter are similar to producing traditional monoclonal antibodies.
• The B cells from immunized transgenic mice are fused with myeloma cells derived
from in vitro cell culture to produce immortalized hybridoma.
• These hybridomas are then screened for desired specificity. Once these specific
hybridomas are produced, it is possible to generate hybrid-hybridomas.
25. Hybrid-hybridoma
• These hybrid-hybridomas are obtained by fusion of two cells which contain the genetic information necessary for
production of two different antibodies. In fact the formation of hybrid-hybridoma paved the first steps towards
humanization of mouse antibodies.
• They can also secrete chimeric antibodies made up of two non-identical halves. This new class of
immunotherapeutic agents is also called bi-specific antibodies.
• This is beneficial in therapeutics as one arm of the bi-specific antibody binds to one antigen, the second arm binds
to another.
• For example one arm of the antibody may bind to a marker molecule and the second to a target cell, creating an
entirely new way of detecting and/or destroying tumor cells.
• This also has potentials in cancer immunotherapy as one arm of this chimeric antibody locks onto the tumor cells
while the other may bind to a killer T cell to activate the destruction of tumor cells.
26. Recombinant antibodies by
cloning v-region genes
• The functional structure of the antigen-binding site is determined by genes of both
heavy (H) and light (L.) variable (V) domains.
• Therefore in this technology, the V domain is extracted from mouse monoclonal
cell lines and cloned into a mammalian expression vector. Then the vector is
transfected into mammalian cells (usually Chinese hamster ovary (CHO) cells]
which can generate the humanized/chimeric antibodies.
• Cloning of mouse variable genes into human constant-region genes generates
chimeric as well as humanized antibodies depending on the size of the clone.
27. Immunotherapeutic in clinical practice
• The WHO appointed body for International Non-proprietary Names (INN)
has given different suffixes to these antibodies to identify their origins,
• Chimeric antibodies (Names-xiMabs)
• Humanized antibodies (Names -zuMabs)
• Fully human antibodies (Names -muMabs)