Antibody-based immunotheranostics for tumor therapy and diagnosis
Immune effector cells (T cells, NK cells) can be cross-linked to tumor cells via antibody (Ab)-based molecules including bispecific Abs (bsAbs). As a result, an immune synapse-like interaction is formed by which immune cells become activated causing tumor cell lysis. Over the past decades, numerous research groups developed different bsAb formats for this purpose. In 2014, the first bispecific T cell engager was approved by the US Food and Drug Administration. Similarly, in our department we develop diverse bsAbs (comprising different formats) that specifically engage T cells to target various hematological as well as solid tumors. 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 acute myeloid leukemia (AML) cells. Both bsAbs were translated in clinical phase I trials. In addition, our group established an Ab-based modular platform technology. In this “modular system“, a bsAb functions as effector module (EM for T cell engagement) that can be combined with a target module (TM for tumor targeting). The resulting immune complex of effector and target module is able to functionally replace conventional bsAbs. The modular character of this technology allows an accelerated development of Ab-based tools for flexible targeting of different tumor antigens in order to overcome tumor heterogeneity and tumor escape variants. Furthermore, the combination with TMs, that additionally provide e.g. costimulatory domains, can modulate the immunosuppressive microenvironment of solid tumors in a beneficial way for immunotherapy efficacy. Besides immunotherapy, the same TMs can be radiolabeled and used for diagnostic imaging (see also Radioimmunotherapy).