immunosuppressive antibodies
TRANSCRIPT
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