Mabs' drug

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Monoclonal Antibodies Drugs

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Mabs' drug

  1. 1. - Aarati K.C - Chhabi Acharya B.Pharmacy HOPE Int’l College Monoclonal Antibodies' Popular Drugs
  2. 2. We will discuss about: • Introduction • History • Types (with example) • Pharmacokinetic profile • Therapeutic uses (with specific drug) • Future Aspect • Conclusion
  3. 3. Introduction: • Monoclonal antibodies (mAb or moAb) are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell. • Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope. • Monoclonal antibodies that specifically bind to substance; they can then serve to detect or purify that substance. • This has become an important tool in biochemistry, molecular biology and medicine.
  4. 4. History: • 1975: Hybridoma Technology George Kohler and Cesar Milstein devised a method to obtain large amounts of a mAb • 1984: Noble prize for medicine • 1988: Greg winter et. al pioneered the techniques to humanize monoclonal antibodies Cesar Milstein & George Kohler
  5. 5. Types of mAb: • Murine • Chimeric mAb • Humanized mAb • Human mAb
  6. 6. 1.Murine: • Derived from mice murinae. • Patients treated with murine mAbs develops human antimouse antibodies(HAMA) • Rapid clearance of the mAbs. • Poor tumor penetration. • Hypersentivity reaction.
  7. 7. 2.Chimeric mAbs: • Antigen binding parts(variable region) of mouse Ab with effector parts (constant region)of human • E.g.: - Infliximab - Abciximab - Rituximab
  8. 8. 3.Humanized mAb: • Human antibody with complimentary determining region(CDR) or hyper variable region from non human sources • E.g.: - Daclizumab - Trastuzumab
  9. 9. 4. Human mAb: • Human monoclonal antibodies are produced using transgenic mice. • Human monoclonal antibodies are produced by transferring human immunoglobulin genes into the murine genome, after which the transgenic mouse is vaccinated against the desired antigen, leading to the production of monoclonal antibodies, allowing the transformation of murine antibodies in vitro into fully human antibodies.
  10. 10. Pharmacokinetics: • Routes of administration: - Subcutaneously: Rituximab, trastuzumab, adalimumab - Intramuscularly: Palirizumad • Half-life: - Chimeric: 4-15 days - Humanized: 3-24 days - Recombinant human:11-24days - Human antimouse antibody (HAMA) response develops 7-10 days following exposure to murine antibody.
  11. 11. Therapeutic Uses: 1. Immuno Suppression - Autoimmune diseases 2. Malignancies 3. Antiplatelet therapy 4. Asthma 5. Osteoporosis
  12. 12. 1.Immuno suppression: • Muromonab: CD-3-murine mAbs • 1st mAb approved for clinical use in humans. • Act on CD3 receptors. • Apoptosis of the T-cell. • Prevents graft rejection in renal transplant. • ADRs: Skin reaction, fever, chills, headaches, nausea, and diarrhea etc.
  13. 13. Autoimmune disease • Epratuzumab: - Humanized antibodies that binds to the glycoprotein CD22 of mature and malignant B-cells. • Efalizumab: - Humanized antibody that binds with CD11 a subunit of lymphocytes function associated antigen 1. - Therapeutic uses: Plague psoriasis. - ADR: Bacterial sepsis, viral meningitis, invasive fungal disease
  14. 14. 2.Magligencies: • Rituximab: First chimeric IgG-I mAb Mechanism of action: Directed against CD 20 on B cells. • Cetuximab: Chimeric Ab Directed against EGFR Inhibits tumor growth - Therapeutic use: Metastatic colorectal cancer, head and neck cancer. • Bevacizumab: Humanized mAb - MoA: Directed against VEGF Blocks VEGF in neovascularisation.
  15. 15. - Therapeutic uses: Metastatic colorectal ca, Pancreatic ca, Breast cancer Prostate cancer. • Trastuzumab: Humanized Ab. - Therapeutic uses: Metastatic breast cancer.
  16. 16. 3.Antiplatelet therapy: • Abciximab: Chimeric mAb • MOA: - Glycoprotein iib/iiia receptor antagonist. - Prevent platelet aggregation - Inhibits fibrinogen • Therapeutic uses: - Acute coronary syndrome - PCI • ADR: - Increase risk of bleeding, thrombocytopenia.
  17. 17. 4.Asthma • Omalizumab: Humanized Ab • MOA: - Binds IgE - Interaction with basophils and mast cells. • Therapeutic uses: Asthma in adults and adolescents refractory to inhaled corticosteroid therapy.
  18. 18. 5.Osteoporosis: • Denosumab: Human mAb • Act against rank ligand • Approved by FAD for use in postmenopausal women with risk of osteoporosis. • ADR: Urinary tract infection, constipation, rashes and joints pain.
  19. 19. Future aspect: • Lpilimumab: Human monoclonal antibodies. • Undergoing clinical trials treatment of melanoma • Zanolimumab: CD4 specific mAb • Cutaneous T-cell lymphoma • Phase iii clinical trial • Others uses: Diagnostics: • HIV diagnostics kit • A mAb can be used to detect pregnancy only 14 days after conception. • Other mAb allow rapid diagnosis of hepatitis.
  20. 20. Conclusion: • MAbs are highly specific Abs produced by a clone of single hybrid cells formed by fusion of B cell with the tumor cell. • The hybridoma formed yields higher amount of MAbs. MAbs can be produced in vitro and in vivo . • Recombinant DNA technology, genetic engineering and transgenic animals are used to produce humanized MAbs or pure human MAbs, with fewer ADRs Used for treatment of cancer, autoimmune disorders, graft rejections, infections, asthma etc.
  21. 21. References: • Dr. Haramjit Singh, Monoclonal antibodies and their role in pharmacology, 19th July 2012 • http://www.imgt.org/IMGTrepertoire/GenesClinical/mon • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC287422/

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