Monoclonal Antibodies and their role in Pharmacology
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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.
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Monoclonal Antibodies and their role in Pharmacology
- 1. MONOCLONAL ANTIBODIES AND THEIR ROLE IN PHARMACOLOGY Dr.Harmanjit Singh PG Resident (pharmacology) GMC, Patiala
- 7. HGPR T – HYPOXANTHINE GUANINE PHOSPHORIBOSYL TRANFERASE HAT – HYPOXANTHINE, AMINOPTERIN, THYMIDINE
- 12. EVOLUTION OF MONOCLONAL ANTIBODY 1. TRANSGENIC 2. LIBRARIES a.BACTERIOPHAGE b. mRNA c. Cell Surface Ist generation mab 2 nd generation mab daclizumab
- 13. Types of mAbs Purple denotes human component orange murine component
- 18. Nomenclature of Monoclonal Antibodies Prefix Target Source Suffix variable -o(s)- bone -u- human -mab -vi(r)- viral -o- mouse -ba(c)- bacterial -a- rat -li(m)- immune -e- hamster -le(s)- infectious lesions -i- primate -ci(r)- cardiovascular -xi- chimeric -mu(l)- musculoskeletal -zu- humanized -ki(n)- interleukin -axo- rat/murine hybrid -co(l)- colonic tumor -me(l)- melanoma -ma(r)- mammary tumor -go(t)- testicular tumor -go(v)- ovarian tumor -pr(o)- prostate tumor -tu(m)- miscellaneous tumor -neu(r)- nervous system -tox(a)- toxin as target
- 23. List of some important Mabs Therapeutic agent Indication Alemtuzumab B cell CLL Bevacizumab Met. Colon cancer Ranibizumab Neovas. Macular degenration Cetuximab Met. Colon cancer Gemtuzumab AML Panitumumab Colorectal cancer Rituximab Low grade NHL Trastuzumab Met. Breast cancer
- 24. Therapeutic agent Indication Abatacept Severe RA Basiliximab, Renal, heart transplant Daclizumab Renal transplant, M.Sclerosis Efalizumab Psoriasis Adalimumab RA Abciximab ACS Omalizumab Allergic asthma Palivizumab RSV infection Natalizumab M.Sclerosis
Notas do Editor
- The functional groups of the paratope (Fab) interact with the epitope (antigen) Hydrogen bonding Van der Waals forces Ionic interactions The CDRs are necessary for antigen binding The tertiary structure of this region can contain pockets, undulating flatter surfaces, and even protrusions Small antigens typically bind in deep pockets
- Antibodies have two major functions: • They recognize and bind antigens • They induce immune responses in the host organism after binding an antigen 14 The two functions of an antibody correlate with the two major regions of the antibody. Variable Region: The amino acid sequence in the tips of the “Y” varies greatly among different antibodies. This variable region, composed of 100-110 amino acids, gives the antibody its specificity for binding antigen. The variable region includes the ends of the light and heavy chains. Treating the antibody with a protease can cleave this region, producing Fab (fragment, antigen binding) that include the variable ends of an antibody. The specificity that an antibody shows for a given antigen is absolute. To date, nothing else developed for therapeutic purposes has shown this kind of specificity. 14 Constant Region: The amino acid sequence in the rest of the antibody is conserved and exhibits low variability among different antibodies. Different classes of constant regions in the stem of the antibody generate different isotypes with differing properties based on their amino acid sequence. Antibodies are divided into five major classes, IgM, IgG, IgA, IgD and IgE, based on their constant region structure and immune function. These classes differ in the mechanism used to destroy antigen. 14
- The ongoing success of existing products, combined with a bulging pipeline of new products awaiting approval and limited generic erosion, point towards robust growth in this segment
- 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 variable region framework Recombinant monoclonal antibodies . Recombinant antibody engineering involves the use of viruses or yeast to create antibodies, rather than mice. Phage display library: construction of V H and V L gene libraries and expression of them on a filamentous bacteriophage. The phage expressing an antigen-bonding domain specific for a particular antigen to screen the mAbs
- ICAM -1 intercel adhesion molecule rogressive multifocal leukoencephalopathy (PML) LFA-1 leukocyte fxn associated ag
- cytokine syndrome: skin reactions, fatigue , fever , chills , myalgia , headaches , nausea and diarrhea T cells recognise antigens primarily via the T cell receptor . This receptor needs various co-receptors to function, one of which is CD3. The T cell receptor-CD3 complex transduces the signal for the T cell to proliferate and attack the antige
- rash rarely leads to dose reductions or termination of therapy. It is generally reversible after treatment is finished and may also be associated with a good response to therapy. [5]
- pretreatment with diphenhydramine 30-60 min. before administration is standard of care