Effector Cell Recruitment by Bispecific Antibodies

Abstract

Bispecific antibodies comprising two binding sites with different specificities in one single molecule offer an elegant approach to improve antibody therapy. For redirecting cytotoxic effector cells against tumors, typically the first binding site of a bispecific antibody recognizes a tumor-associated antigen, whereas the second site engages a stimulatory trigger molecule on effector cells. The adequate choice of the trigger molecule offers the opportunity to attract a defined pool of effector cells and may improve recruitment of Fc receptor-expressing cells such as monocytes/macrophages, granulocytes, or NK cells. Additionally, bispecific antibodies allow redirection of T lymphocytes which lack Fc receptors and therefore are not recruited by conventional antibodies. Meanwhile bispecific T cell engaging antibodies revealed therapeutic potential in clinical trials. This chapter outlines the concept of bispecific approaches in cancer immunotherapy, introduces candidate trigger molecules on different effector cell populations, and summarizes preclinical and clinical data obtained with bispecific antibodies.