Anti-GPRC5D-Anti-BCMA-Anti-CD3 Trispecific Antibody (Ramantamig)

Ramantamig, also known as JNJ-79635322, is a humanized monoclonal antibody that targets human CD3epsilon, GPRC5D, and BCMA (TNFRSF17). Ramantamig can binds to BCMA and GPRC5D on cancer cells and CD3epsilon on T cells. This leads to the formation of immunological synapses, and enables T-cell-mediated cytotoxicity. Ramantamig carries mutations to reduce interaction with Fc receptors and disrupt protein A binding of monomeric and homodimerized chains. This trispecific antibody is produced in a CHO stable cell line. G protein-coupled receptor class C group 5 member D (GPRC5D) is an orphan receptor of little-known function belonging to the large family of G protein-coupled receptors. The protein is highly expressed in malignant plasma cells such multiple myeloma and is now considered a therapeutic target for antibody-based treatment of multiple myeloma (MM). For example, CAR (chimeric antigen receptor)-T cells and GPCR5DxCD3 bispecific antibodies are under development. B-cell maturation antigen (BCMA), also known as CD269 or tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a cell surface receptor of the TNF receptor superfamily that recognizes B-cell activating factor (BAFF). BCMA is preferentially expressed in mature B lymphocytes and on MM cells. BCMA is a highly attractive target antigen for immunotherapy because of its restricted expression in nonmalignant tissue but almost universal expression on MM cells. The development if trispecific antibodies targeting both GPRC5D and BCMA can enhance tumor binding avidity and specificity. One example is Ramantamig, which is being studied in models of MM.