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Monoclonal antibodies dr.elza

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Monoclonal antibodies

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Monoclonal antibodies dr.elza

  1. 1. MONOCLONAL ANTIBODIES By Dr. Elza Joy Munjely JR III Dpmt of Pharmacology Govt.Medical College,Kottayam
  2. 2. Those antibodies which are produced by a single clone of B lymphocytes and are directed against a single antigenic determinant
  3. 3. How are they made? Hybridoma technology Hybridoma = Specific B-lymphocyte + Mouse myeloma cell • Retains the antibody forming ability of B-lymphocyte & the ability of myeloma cell to proliferate endlessly
  4. 4. Hybridoma Technology 1975, Georges Köhler and Cesar Milstein - Nobel Prize in1984
  5. 5. Mouse immunized with antigen X Spleen cells Cell-culture Myeloma line Myeloma cells Fused in Polyethylene Glycol to produce Hybridomas Transfered to HAT mediumUnfused plasma & myeloma Cells die Hybridomas that produce antibodies specifically against Antigen X are selected & Grown in bulk Monoclonal antibodies
  6. 6. Light chain Heavy chain Variable regions Of heavy & Light chains Constant regions Of heavy & Light chains ANTIBODY
  7. 7. Classification Murine Chimeric Humanised Human Highly immunogenic Least immunogenic 100% mouse 30% mouse 5-10% mouse 100% human
  8. 8. Nomenclature • tu - tumour • vi - virus • ci - circulation • If no prefix - immunomodulator Murine Chimeric Humanised Human omab ximab zumab umab
  9. 9. Examples Murine Chimeric Humanised Human omab ximab zumab umab •Muromonab •Rituximab •Abciximab •Infliximab •Alemtuzumab •Bevacizumab •Trastuzumab •Omalizumab •Palivizumab •Adalimumab
  10. 10. Armed & unarmed monoclonal Abs ‘Unarmed / Naked’ Armed Not fused to a toxin Fused with a toxin or a radioisotope Acritumomab - labeled with Technetium 99 immunoscintigraphy Ibritumomab - labeled with Yttrium 90 relapsed/refractory low grade follicular/B-cell NHL
  11. 11. Mechanisms of anti-tumour effects of MAbs • ADCC-Antibody dependent cellular cytotoxicity • CDC-Complement dependent cytotoxicity • Immunomodulation • Altering signal transduction
  12. 12. Pharmacokinetics • Routes of administration: – Subcutaneously (Rituximab, Trastuzumab, Adalimumab) – Intramuscularly (Palivizumab) – Intravenously • IV route: preferred because of 100% bioavailability • Route for elimination of antibodies – Via uptake & catabolism by reticuloendothelial system & target tissue.
  13. 13. • Patients treated with murine mAbs develop a Human Antimouse Antibody (HAMA) response which develops 7– 10 days following exposure to murine antibody – Rapid clearance of the mAb – Poor tumour penetration – Hypersensitivity reactions • Half-life – Chimeric : 4 –15 days – Humanized: 3 - 24 days – Recombinant human: 11– 24 days Pharmacokinetics
  14. 14. • Allergic reactions, such as hives or itching • Flu-like symptoms, including chills, fatigue, fever, muscle aches and pains • Nausea • Diarrhea • Skin rashes • Infection - infliximab • Bone marrow suppression • Cardiomyopathy – Trastuzumab • Thromboembolism - Bevacizumab Side effects of monoclonal antibody
  15. 15. Uses of Mabs THERAPEUTIC USES Malgnancies Auto immune disease Asthma DIAGNOSTIC APPLICATONS In western blot, ELISA, RIA, flow cytometry, Immunodot blot, pregnancy detection etc.
  16. 16. THERAPEUTIC CLASSIFICATION 1. Antitumor MABs 2. MABs Used to Deliver Isotopes & Toxins to Tumors 3. MABs Used as Immunosuppressants & Anti- Inflammatory Agents 4. Other MABs
  17. 17. Antitumor MABs MABs Used to Deliver Isotopes & Toxins to Tumors MABs Used as Immunosuppressa nts & Anti- Inflammatory Agents 1. Alemtuzumab 2. Bevacizumab 3. Cetuximab 4. Panitumumab 5. Rituximab 6. Trastuzumab Toxin-linked MAbs : • Gemtuzumab ozogamicin Radioisotope carrying MAbs : •Ibritumomab (90Y) •Tositumomab (131I) 1. Muromonab-Anti CD-3 antibody 2. Daclizumab, Basiliximab-IL-2 receptor antagonists 3. Infliximab, Adalimumab- TNFα inhibitors: 4. Omalizumab- Anti-IgE antibody
  18. 18. List of some important Mab Therapeutic agent Indication • Alemtuzumab (CD52) B cell CLL • Bevacizumab (VEGF) Met. Colorectal cancer • Ranibizumab (VEGF-A) Neovas. Macular degeneration • Cetuximab (EGFR) Met. Colorectal cancer • Gemtuzumab (CD33) AML • Panitumumab (EGFR) Met. Colorectal cancer • Rituximab (CD20) Low grade NHL • Trastuzumab (HER-2/neu) Met. Breast cancer • Eculizumab (C5) PNH
  19. 19. List of some important Mab Therapeutic agent Indication • Basiliximab (IL-2 Receptor) Renal, heart transplant • Daclizumab (IL-2 Receptor) Renal transplant, M.Sclerosis • Efalizumab (CD11a) Psoriasis • Adalimumab (TNF α) RA • Infliximab (TNF α) RA • Abciximab (GPIIb/IIIa receptor Acute coronary syndrome on activated platelets) • Omalizumab (IgE Ab) Allergic asthma • Palivizumab RSV infection • Natalizumab (integrins) M.Sclerosis,Crohn’s disease
  20. 20. Thankyou

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