This document provides an overview of monoclonal antibodies (mAbs), including their structure, production, and applications. It discusses how mAbs are produced through cell fusion techniques, screened for the desired specificity, and cloned. The document outlines the different types of mAbs that have been designed, such as chimeric and humanized mAbs, to reduce immunogenicity. It also describes how mAbs can be used for targeted drug delivery through conjugation to drugs, toxins, or radioisotopes. In summary, the document gives a comprehensive introduction to monoclonal antibodies, from their production and characterization to their uses in therapy and diagnostics.
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Brief description of targeted drug delivery system, along with its concept and strategies for drug targeting. Advantages and disadvantages of drug targeting
Need for drug targeting.
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Brief description of targeted drug delivery system, along with its concept and strategies for drug targeting. Advantages and disadvantages of drug targeting
Need for drug targeting.
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
Various approaches to Targeted Drug Delivery Systems (TDDS) in its formuation and evaluation in a pharmaceutical industry and research is outlined in this presentation.
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
Various approaches to Targeted Drug Delivery Systems (TDDS) in its formuation and evaluation in a pharmaceutical industry and research is outlined in this presentation.
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
Students of medical and allied subjects must be exposed to the concept of monoclonal antibodies for the efficient practice of clinical and laboratory medicine.
Hybridoma Technology ( Production , Purification , and Application ) Sakshi Ghasle
Hybridoma technology revolutionized the field of immunology by enabling the production of monoclonal antibodies with high specificity and affinity. This presentation delves into the principles of DNA hybridoma technology, highlighting its significance in antibody production, therapeutic applications, and biomedical research. Learn about the key steps involved in generating hybridomas, from immunization to antibody screening, and discover the potential of recombinant DNA techniques in enhancing antibody engineering. Whether you're a student, researcher, or industry professional, this overview will provide valuable insights into the innovative world of hybridoma technology."
Uncover the wide-ranging applications of monoclonal antibodies in areas such as cancer therapy, autoimmune diseases, infectious diseases, and beyond. Learn about the latest advancements in antibody engineering and the development of novel therapeutic modalities, including bispecific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors.
Whether you're a seasoned researcher or a newcomer to the field, this SlideShare presentation serves as a valuable resource for understanding the principles, techniques, and applications of hybridoma technology in modern biomedicine. Join a journey through the fascinating world of monoclonal antibodies and the groundbreaking science behind their creation.
Unlock the potential of hybridoma technology and propel your research to new heights. Dive into this SlideShare presentation now and explore the limitless possibilities of monoclonal antibody production with hybridoma technology.
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!
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
2.
INTRODUCTION
STRUCTURE OF ANTIBODIES
HISTORY OF AB
ANTIGEN-AB BINDING
PRINCIPLE INVOLVED FOR MAB
MAB FOR TUMOUR TARGETING
LIMITATION
REFERENCES
Contents
3.
INTRODUCTION
Antibodies are produced by a specialized group of cells
called B-Lymphocytes.
When an foreign antigen enters the body due immune
response B-Lymphocytes develops into plasma cells and
liberates antibodies or immunoglobulin's of various
types(Ig A, Ig D, Ig E, Ig G, Ig M).
3
4. IgG: IgG1 (66%), IgG2 (23%), IgG3 (7%) and IgG4
(4%) , blood and tissue liquid
IgA: IgA1 (90%) and IgA2 (10%), external secretions
(stomach, intestines, saliva, tears, etc.)
IgM: 5-10% of total serum Ig [1.5mg/ml serum
conc.]
IgD: 1% of proteins in the plasma membranes of B-
lymphocytes, function unknown [30µg/ml serum
conc.] 0.2% of total serum Ig
IgE: 0.3µg/ml on the surface of plasma membrane of
mast cells, play a role in immediate hypersensitivity
and denfense for parasite
Classes of Igs
5. 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 (mAb) are antibodies that
are identical because they were produced by one
type of immune cell, all clones of a single parent
cell.
Polyclonal antibodies are antibodies that are derived
from different cell lines. They differ in amino acid
sequence.
What are antibodies?
6.
• Each Antigen has specific antigen determinants
(epitopes) located on it. The antibodies have
complementary determining regions (CDRs). These
are mainly responsible for the antibody specificity.
• Each antigen has several different epitopes on it.
They are recognised by many different antibodies.
All these antibodies thus produced act on the same
antigen. Hence these are designated as polyclonal
antibodies.
6
7.
• In general naturally produced antibodies are non-
specific and heterogenous in nature. Hence there are
several limitations in the use of polyclonal antibodies
for therapeutic and diagnostic purposes.
• Thus there is a need for producing monoclonal
antibodies for different antigens.
7
11. Types of mAbs designed
• Murin source mAbs:: rodent mAbs with excellent
affinities and specificities, generated using conventional
hybridoma technology. Clinical efficacy compromised by
HAMA (human anti murine antibody) response, which
lead to allergic or immune complex hypersensitivities.
• Chimeric mAbs:: chimers combine the human
constant regions with the intact rodent variable regions.
Affinity and specificity unchanged. Also cause human
antichimeric antibody response (30% murine resource)
• Humanized mAbs:: contained only the CDRs of the
rodent variable region grafted onto human Framework
Regions [FR]
12. Human mAb :: three currently available approaches to the
production of human monoclonal antibodies are described. These
include :-
the hybridoma technique, based on the fusion of antibody-
producing human B lymphocytes with either mouse or human
myeloma or lymphoblastoid cells;
the EBV immortalization technique, based on the use of Epstein-
Barr virus (EBV) to immortalize antigen-specific human B
lymphocytes;
the EBV-hybridoma technique, based on a combination of the first
two methods.
The EBV-hybridoma system retains the advantageous features of the
other two systems while overcoming their pitfalls and may be the
current method of choice for producing human monoclonal
antibodies with a defined specificity.
Types of mAbs designed . .
15.
Hybridoma technology: In this B-Lymphocytes and
myeloma cells are mixed together and exposed to
PEG for a short period.
The mixture contains hybridoma cells, myeloma cells
and lymphocytes.
This mixture is washed and cultured in
HAT(hypoxanthine aminopterin and thymidine)
medium for 7-10 days.
only hybridoma cells remain in the mixture.
15
16. Immunise
Spleen Cell Myeloma Cell Line
FUSE
HAT sensitive
Hybridoma
HAT resistant
Stable hybrid myeloma producing desired antibody
SELECT
16
18.
Immunization
Cell fusion
Selection of hybridomas
Screening the products
Cloning and propagation
Characterization and storage
18
19.
Immunize an animal usually mouse by injecting with an
appropriate antigen along with Freund’s complete or incomplete
adjuvant.
Adjuvants are non specific potentiators of specific immune
responses.
Injection of antigens at multiple sites are repeated several times
for increased stimulation of antibodies.
3 days prior to killing of animal a final dose is given
intravenously.
Spleen is aseptically removed and disrupted by mechanical or
enzymatic methods to release the cells.
By density gradient centrifugation lymphocytes are separated
from rest of the cells.
19
20.
Lymphocytes are mixed with HGPRT deficient
myeloma cells and is exposed to PEG for a short
period.
The mixture is then washed and kept in a fresh
medium.
The mixture contains hybridomas, free myeloma
cells, and free lymphocytes.
20
22.
The above mixture is cultured in HAT medium for 7-10 days.
Due to lack of HGPRT enzyme in myeloma cells, salvage
pathway is not operative and aminopterin in HAT medium
blocks the de novo synthesis of nucleotides. Hence free
myeloma cells are dead.
As the lymphocytes are short lived they also slowly dissappear.
Only the hybridomas that receives HGPRT from lymphocytes
are survived.
Thus hybridomas are selected by using HAT medium
Suspension is diluted so that each aliquot contains one cell each.
These are cultured in regular culture medium, produced desired
antibody.
22
23. The hybridoma technology:
Spleen cells from immunized mice are fused with the murine myeloma
cells.
Several process had been developed at large scale.
According to the different cell culture methods, it can calisifed into four
fields
1. Robottle cell culture process.
2. Membrane binded cell culture process
3. Microcarrier cell culture process
4. Suspended cell culture process
Conventional production of mAbs
24.
Screening is done for antibody specificity.
For this we need to test the culture medium from each
hybridoma culture for desired antibody specificity.
Common tests like ELISA and RIA are used for this.
In these tests the antigens are coated to plastic plates. The
antibodies specific to the antigens bind to the plates. The
remaining are washed off.
Thus the hybridomas producing desired antibodies are
identified. The antibodies secreted by them are
homogenous and specific and are referred as monoclonal
antibodies.
24
25.
The single hybrid cell producing the desired antibody are
isolated and cloned.
Usually two techniques are commonly employed for this
a) Limiting dilution method: Suspension of hybridoma
cells is serially diluted so the aliquot of each dilution is
having one hybrid cell. This ensures that the antibody
produced is monoclonal.
b) Soft agar method: In this method the hybridoma cells
are grown in soft agar. These form colonies and the
colonies are monoclonal in nature.
25
26.
Biochemical and biophysical characterization are
made for desired specificity.
It is important to note the monoclonal antibody is
specific for which antigen
MAbs must be characterized for their ability to
withstand freezing and thawing.
26
27.
Encapsulating the hybridoma cells in alginate gels
and using a coating solution containing poly-lysine is
employed.
These gels allow the nutrients to enter in and
antibodies to come out.
Damon biotech and cell-tech companies are using this
technique for commercial production of MAbs.
They employ 100-litres fermenters to yield about 100g
of MAbs in about 2 weeks period.
27
28.
MAbs derived from mouse are murine derivatives.
As they are not human origin, they show
HAMA(human antimouse antibody) response.
To overcome this we need to cleave the antibody into
its respective Fc and Fab fragments.
Fab fragments are less immunogenic and their
smaller molecular size may facilitate penetration into
tumor tissue and result in a longer half-life.
Engineering is needed to reduce the immunogenicity.
28
29.
Chimeric antibodies:
Hence the murine antibodies are immunogenic to
humans, the obvious solution for this is to clone a
fully human antibody. But it has many problems like
ethical clearance, difficult to culture, impossible to
obtain many of the appropriate antibodies.
To over come HAMA(human antimouse antibody)
response, a chimeric antibody is prepared with Fc
region of human IgG and Fab regions of murine
origin by the use of DNA recombinant technology.
29
31.
Humanized antibodies:
Though chimeric antibodies elicit less HAMA response
than murine antibodies, they are still immunogenic due to
their murine regions(30%)
It is came to know that a small portion(CDR) of an
antibody was actually responsible for antigen binding.
By this humanized antibodies are prepared by
recombinant DNA technology with majority of human
antibody framework and CDR’s of murine antibody.
Thus humanized antibodies are 95% homology with
human antibodies.
31
33.
Bispecific antibodies:
These are specific to two types of antigens.
They are constructed by r.DNA technology.
Each arm is specific to one type of antigen.
33
34.
Immunoconjugate:
For MAb targeted drug delivery, a drug is bound
covalently to an antibody that is chosen to target it to the
desired site of action.
Spacer is present between the antibody and the drug.
Polymer may be present to increase the no. of drug
molecules attached to the antibody.
Drug is non-covalently incorporated into a liposome or
microsphere to which the targeting antibody is bound to
the surface—immunoliposome or immunomicrosphere
resp.
34
35.
Principle involved:
As several classes of the drugs lack specificity for diseased
cells, they show their action on other sites of action.
Ex: cytotoxic action of chemotherapeutic agents is directed
against any rapidly proliferating cell population.
Hence drug targeting is required to overcome this
problem.
Targeting is classified into three categories:
1. Passive targeting
2. Physical targeting
3. Active targeting
35
36.
It is the natural in-vivo distribution pattern of the
drug delivery system. It is determined by the
inherent properties of the carrier like hydrophobic
and hydrophilic surface characteristics, particle size,
surface charge, particle number.
Ex: passive targeting of the lungs is made by
modulating the size of the particles to >7µm
passive targeting of the Reticuloendothelial system is
made by modulating the size of the particles to 0.2-
7µm
36
37.
In this some characteristics of the environment are
utilized for the carrying of the drug to the specific
site.
Ex: thermal sensitive liposomes(local hyperthemia)
magnetically responsive albumin microspheres
(localized magnetic field)
37
38.
Active targeting is usually done by cell-specific
ligands. These are specific to specific cell types. But it
is limited to small no. of tumor types.
Hence MAb targeting is adopted for active targeting.
MAb targeting is done by conjugating the drug
antibody of the specific targeting type.
Hence antibody drug conjugates are used as active
targeting drug delivery systems.
38
39.
Toxin conjugates (immunotoxins)
EX: diphtheria toxin, Ricin have been conjugated to
the tumor specific antibodies
Ricin has two chains. Amoung these A-chain is
cytotoxic and B-chain is non-specific. Hence B-chain
is removed and the toxin is conjugated to tumor
specific antibody. Thus we increase the specificity of
the toxins by using MAbs as active drug targeting
systems.
39
40.
Drug immunoconjugates:
Agents like chlorambucil, methotrexate and
doxorubicin are conjugated with tumor specific
antibodies.
Ex: doxorubicin-BR96 immunoconjugate for Lewis
antigen found on the surface of tumor cells.
40
41.
They are homogenous in nature.
They are specific to a particular antigen with a
particular epitope.
Ex:Rituximab (Rituxan®, anti-CD20) is a good
example – this antibody is used for the treatment of
lymphoma.
41
42.
The first approved mAbs was OKT-3 [1986], which is a
murine IgGa2 protein to deplete T cells in patients with
acute rejection of renal allotransplant.
FDA Approval
43. Prevents acute
rejection of kidney
transplants
Prevents
autoimmune
destruction of islet
cells in type I
Diabetes mellitus
OKT3
47.
As they are specific to a particular antigen, they cannot distinguish
molecule as a whole.
Some times they cannot distinguish groups of different molecules.
Ex:- presence of retro viruses as a part of mammalian chromosomes
is not distinguished.
Mice used in MAb production carry Adenovirus, Hepatic virus,
Retrovirus, reovirus, cytomegalovirus, thymic virus.
The presence of some of these viruses is detected in hybridomas.
This poses a great danger since there is no guarantee for MAb
produced is totally virus free.
For this reason US food and drug administration insists that MAb
for human use should be totally free from all pathogenic organisms
including viruses.
47
48.
Biotechnology by U. Satyanarayana
Harper's Biochemistry 26th edition
www.wikipedia.com
www.google.com
48