Immune effector cells (T cells) can be specifically cross-linked with tumor cells via bispecific antibodies (bsAbs). Thereby, bsAbs induce the formation of an immune synapse-like structure that results in activation of the immune cells and subsequently in tumor cell lysis. Over the past decades, numerous research groups developed different bsAb-formats for this purpose. Recently (2014), the first bispecific T cell engager (BiTE) was approved by the US Food and Drug Administration in a so-called fast-track procedure.
Similar to this format, we also developed different BiTEs that specifically engage T cells for tumor cell killing. Among them one is directed against the prostate stem cell antigen (PSCA) overexpressed on prostate cancers (but also e.g. on breast and pancreas carcinomas), another one binds to CD33 which is highly expressed on tumor cells of patients with acute myeloid leukemia (AML). Both BiTEs are close to clinical translation.
Besides the development of conventional BiTEs, we further established an Ab-based modular platform technology. For this purpose, a bispecific effector module was designed that can be combined with different target modules (see also Cellular Immunotherapeutics). The resulting immune complex of effector and target module is able to functionally replace conventional BiTEs. The modular character of this technology allows not only an accelerated development of bsAbs, but also the combination with TMs that additionally provide e.g. costimulatory domains for modulation of the immunosuppressive microenvironment of solid tumors.References: