anti-CD37 bispecific monoclonal antibody GEN3009

An Fc-engineered, humanized, bispecific hexamer formation-enhanced immunoglobulin (Ig) G1 monoclonal antibody that targets two separate epitopes on the tumor-associated antigen (TAA) CD37, with the E430G hexamerization-enhancing mutation, with potential immunomodulating and antineoplastic activities. Upon administration, the anti-CD37 bispecific monoclonal antibody GEN3009 specifically targets and binds to two non-overlapping CD37 epitopes, thereby inducing an assembly of antibody hexamers through intermolecular Fc-Fc interactions at the cell surface of CD37-overexpressing tumor cells. These hexamers recruit and activate C1, the first component of complement, thereby triggering the complement cascade which activates the immune system to induce complement-dependent cytotoxicity (CDC). In addition, GEN3009 binding to the CD37-overexpressing tumor cells also causes antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). CD37, a member of the tetraspanin superfamily of cell surface antigens, is expressed at high-levels on B cells and to a lesser extent on T cells and myeloid cells. The E430G mutation in the Fc domains enhances Fc-mediated IgG hexamerization upon cellular target binding, and enhances CDC.