Figure 1

FBTA05 (anti-CD3 x anti-CD20 trAb) – mode of action. In a MHC-independent manner polyclonal T cells are redirected to and activated at tumor cells by trAb-mediated recognition of CD3 and tumor-associated antigens (TAAs) such as CD20. At the same time or subsequently FcγR-positive accessory cells such as monocytes/macrophages, dendritic cells (DCs) or natural killer cells interact with the Fc part of trAbs. Through this cellular crosstalk all participating immune cells are strongly activated. Hence, T cells receive a second co-stimulatory signal, while accessory immune cells are stimulated via FcγR crosslinking which leads to the release of proinflammatory cytokines. Thus, tumor cells are effectively eliminated by a concerted attack of cytotoxic T cells and accessory immune cells using different killer mechanisms such as ADCC, phagocytosis, or perforin/granzyme-mediated lysis and apoptosis induction. Finally, T cell proliferation occurs as does phagocytosis of necrotic/apoptotic tumor particles which are then processed, and presented by stimulated professional antigen presenting cells (i.e. DCs), an important prerequisite for the induction of long-lasting vaccination-like effects against tumors. ADCC (antibody dependent cellular cytotoxicity); CMC (complement-mediated cytotoxicity); DC-CK1 (Dendritic cell cytokine 1); IL (interleukin); LFA (leukocyte function-associated antigen); TNF-α (Tumor necrosis factor α).