immunosuppressive antibodies

Immunosuppressive Antibodies

By: Dr. Vahid NikouiEmail: nikoui@razi.tums.ac.ir

History

*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

Polyclonal

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)

IGIV

*High dose (2g/kg)

*Decreased T-Helper and increased T-Suppressor

*In different autoimmune diseases

Rhogam

*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

Hyperimmune IGs

*IGIV

*From selected donors

*Abs against viruses and toxins

Monoclonal

*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

T-cell receptor directed

antibodies

Muromonab-CD3

*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

* In the 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.

Alefacept

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

*Binds to CD2 on T cells

*Psoriasis

Efalizumab

*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

Alemtuzumab

*Humanized IgG1

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

*Chorionic lymphocytic leukemia

Rituximab

*Chimeric IgG1

*Binds to CD20 on B cells

*Non-Hodgkin`s lymphoma

IL-2 receptor directed

antibodies

Basiliximab

*Chimeric mouse/human antibody

*1998

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

*Prophylaxis of the acute organ rejection after kidney transplantation

Daclizumab

*Humanized antibody

*1998

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

*Prophylaxis of the acute organ rejection after kidney transplantation

TNF-α directed antibodies

*Suppression of IL-1 and IL-6 and leukocyte migration

Adalimumab

*Completely Human IgG1

*Rheumatoid arthritis

*Toxicity: lymphoma

Etanercept

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

*Rheumatoid arthritis

*Toxicity: lymphoma

Infliximab

*Chimeric IgG1

*Rheumatoid arthritis

*Crohn`s disease

*Toxicity: lymphoma

Abatacept

*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

Omalizumab

*Humanized Ab against IgE

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

*Prevents resealing of type I allergic mediators

Thank You