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By: Dr. Vahid Nikoui
Email: nikoui@razi.tums.ac.ir
Immunosuppressive Antibodies
Immunosuppressive Antibodies
Immunosuppressive Antibodies
*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
Immunosuppressive Antibodies
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
*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)
*High dose (2g/kg)

*Decreased T-Helper and increased T-Suppressor

*In different autoimmune diseases
* 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
*IGIV

*From selected donors

*Abs against viruses and toxins
Immunosuppressive Antibodies
*Directed towards exactly defined antigens

*Fewer side-effects
* Humanization
* Fc

* Murine
  * -onab

* Humanized
  * -umab    or -zumab


* Chimeric
  * -imab    or -ximab


* Recombinant Pr attached to Abs
  * -cept
Immunosuppressive Antibodies
Immunosuppressive Antibodies
* 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.
*A recombinant Pr that attached to Fc part of
 human IgG1


*Binds to CD2 on T cells

*Psoriasis
*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
*Humanized IgG1

*Binds to CD52 on B cells, T cells and NK

*Chorionic lymphocytic leukemia
*Chimeric IgG1

*Binds to CD20 on B cells

*Non-Hodgkin`s lymphoma
Immunosuppressive Antibodies
*Chimeric mouse/human antibody

*1998

*Binds to IL-2a receptor's α chain (CD25)

*Prophylaxis of the acute organ rejection after
 kidney transplantation
*Humanized antibody

*1998

*Binds to IL-2a receptor's α chain (CD25)

*Prophylaxis of the acute organ rejection after
 kidney transplantation
*Suppression of IL-1 and IL-6 and leukocyte
 migration
*Completely Human IgG1

*Rheumatoid arthritis

*Toxicity: lymphoma
*A recombinant Pr that attached to Fc part of
 human IgG1


*Rheumatoid arthritis

*Toxicity: lymphoma
*Chimeric IgG1

*Rheumatoid arthritis

*Crohn`s disease

*Toxicity: lymphoma
*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
*Humanized Ab against IgE

*Prevents IgE attachment to Fc receptors on basophils
 and mast cells


*Prevents resealing of type I allergic mediators
Immunosuppressive Antibodies

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Immunosuppressive Antibodies

  • 1. By: Dr. Vahid Nikoui Email: nikoui@razi.tums.ac.ir
  • 5. *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
  • 7. 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
  • 8. *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)
  • 9. *High dose (2g/kg) *Decreased T-Helper and increased T-Suppressor *In different autoimmune diseases
  • 10. * 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
  • 11. *IGIV *From selected donors *Abs against viruses and toxins
  • 13. *Directed towards exactly defined antigens *Fewer side-effects
  • 14. * Humanization * Fc * Murine * -onab * Humanized * -umab or -zumab * Chimeric * -imab or -ximab * Recombinant Pr attached to Abs * -cept
  • 17. * 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.
  • 18. *A recombinant Pr that attached to Fc part of human IgG1 *Binds to CD2 on T cells *Psoriasis
  • 19. *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
  • 20. *Humanized IgG1 *Binds to CD52 on B cells, T cells and NK *Chorionic lymphocytic leukemia
  • 21. *Chimeric IgG1 *Binds to CD20 on B cells *Non-Hodgkin`s lymphoma
  • 23. *Chimeric mouse/human antibody *1998 *Binds to IL-2a receptor's α chain (CD25) *Prophylaxis of the acute organ rejection after kidney transplantation
  • 24. *Humanized antibody *1998 *Binds to IL-2a receptor's α chain (CD25) *Prophylaxis of the acute organ rejection after kidney transplantation
  • 25. *Suppression of IL-1 and IL-6 and leukocyte migration
  • 26. *Completely Human IgG1 *Rheumatoid arthritis *Toxicity: lymphoma
  • 27. *A recombinant Pr that attached to Fc part of human IgG1 *Rheumatoid arthritis *Toxicity: lymphoma
  • 28. *Chimeric IgG1 *Rheumatoid arthritis *Crohn`s disease *Toxicity: lymphoma
  • 29. *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
  • 30. *Humanized Ab against IgE *Prevents IgE attachment to Fc receptors on basophils and mast cells *Prevents resealing of type I allergic mediators