Immunosuppressive Antibodies

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Immunosuppressive Antibodies

  1. 1. By: Dr. Vahid NikouiEmail: nikoui@razi.tums.ac.ir
  2. 2. *Milstein & Kohler in 1975*Hybridoma*Antibody-forming cells fused to immortal plasmacytoma cells*Hybrid cells that are stable and produce the required antibody can be subcloned for mass culture for antibody production
  3. 3. Antilymphocyte (ALG) and antithymocyte (ATG) globulins* Obtained from the serum of animals* Steroid-resistant acute rejection reaction and grave aplastic anemia treatment, delayed hypersensitivity and the graft-versus-host disease (GVHD)* As an adjuvant in ciclosporin therapy* Inhibit T lymphocytes and cause their lysis: * Complement-mediated cytolysis * Cell-mediated opsonization followed by removal of reticuloendothelial cells from the circulation in the spleen and liver
  4. 4. *There are two preparations available to the market: * Atgam ,obtained from horse serum * Thymoglobuline obtained from rabbit serum*High immunogenicity, acute reaction to the treatment, fever and even anaphylaxis (type III)
  5. 5. *High dose (2g/kg)*Decreased T-Helper and increased T-Suppressor*In different autoimmune diseases
  6. 6. * Rh0(D) IgG* Mother Rh- and fetus Rh+* Labor, abortion or ectopic pregnancy (sensitization)* Next pregnancy: Erythroblastosis (heamolytic)* Rho Ab injection to mother 24-72 hrs after the labor of a Rh+ newborn
  7. 7. *IGIV*From selected donors*Abs against viruses and toxins
  8. 8. *Directed towards exactly defined antigens*Fewer side-effects
  9. 9. * Humanization* Fc* Murine * -onab* Humanized * -umab or -zumab* Chimeric * -imab or -ximab* Recombinant Pr attached to Abs * -cept
  10. 10. * Murine anti-CD3* Prevents T-cell activation and proliferation* One of the most potent immunosuppressive substances* To control the steroid- and/or polyclonal antibodies-resistant acute rejection episodes* Also used prophylactically in transplantations* Inthe first few administrations this binding non-specifically activates T-cells, leading to a serious syndrome 30 to 60 minutes later. It is characterized by fever, myalgia, headache, and arthralgia.
  11. 11. *A recombinant Pr that attached to Fc part of human IgG1*Binds to CD2 on T cells*Psoriasis
  12. 12. *Humanized antibody*Binds to CD11a (α part of LFA-1) on T cells*Prevents the interaction between LFA-1 and ICAM-1 on APCs*Severe Psoriasis
  13. 13. *Humanized IgG1*Binds to CD52 on B cells, T cells and NK*Chorionic lymphocytic leukemia
  14. 14. *Chimeric IgG1*Binds to CD20 on B cells*Non-Hodgkin`s lymphoma
  15. 15. *Chimeric mouse/human antibody*1998*Binds to IL-2a receptors α chain (CD25)*Prophylaxis of the acute organ rejection after kidney transplantation
  16. 16. *Humanized antibody*1998*Binds to IL-2a receptors α chain (CD25)*Prophylaxis of the acute organ rejection after kidney transplantation
  17. 17. *Suppression of IL-1 and IL-6 and leukocyte migration
  18. 18. *Completely Human IgG1*Rheumatoid arthritis*Toxicity: lymphoma
  19. 19. *A recombinant Pr that attached to Fc part of human IgG1*Rheumatoid arthritis*Toxicity: lymphoma
  20. 20. *Chimeric IgG1*Rheumatoid arthritis*Crohn`s disease*Toxicity: lymphoma
  21. 21. *A recombinant Pr that attached to Fc part of human IgG*Binds to CD80 or CD86 on APCs*Inhibition of contact to CD28 on T cells*Rheumatoid arthritis
  22. 22. *Humanized Ab against IgE*Prevents IgE attachment to Fc receptors on basophils and mast cells*Prevents resealing of type I allergic mediators

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