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Leveraging 3D antigen design approach, we designed antigens and immunized rodents in order to derive new antibodies that exclusively block the epitope binding surface of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4 also known as CD152) from its ligands CD80 and CD86. We focus on antibody drug-candidates that exclusively block this binding surface domain and do not block adjacent domains.
In 2011 a CTLA-4 antibody was first approved in the U.S. for clinical treatment of late stage melanoma. Revenues from this product sales reached $1.3 billion in 2014. Recently, clinical results of a combination treatment with a PD1 antibody, showed a strong synergy in the treatment of late stage melanoma, both as a first line therapy and as a second line of treatment. The U.S. FDA approved the combination treatment of both antibodies for late stage melanoma. With this synergetic clinical effect of the combination treatment, additional clinical indication for CTLA-4 antibody will be investigated.
T cells or T lymphocytes are a type of lymphocyte (a type of white blood cell) that plays a central role in cell-mediated immunity. T lymphocytes recognize and destroy non self cells, including cancer cells. A natural inhibitory mechanism of binding CTLA-4, a receptor that resides on the cytotoxic T lymphocytes (CTLs) in the lymph node, from its ligands CD80 and CD86, interrupts this destruction. A CTLA-4 antibody which binds to the surface domain of CTLA-4 receptor and its ligands, CD80 and CD86, reverse this inhibition effect over the immune system. By blocking this interaction, the “turning-off” of the cytotoxic reaction is reversed, and allows inhibitory signal transmitted through other pathways to cause the CTLs to destroy the cancer cells.
We plan to initially focus our pre clinical trials on models that address melanoma diseases, alone and in combination treatment with PD1 antibody.