Retargeting T cells and immune effector cells with bispecific antibodies.

Abstract

The development of BiAbs for therapeutic applications in cancer shows promise. As our understanding of effector cell receptor biology for triggering of cytotoxic functions improves and the behavior of TAA and the targeting antibody engagement is elucidated, customized BiAb reagents can be engineered to optimize in vivo or ex vivo arming of T cells for targeting tumors. Additionally, other variables that require consideration in the equation for successful T cell immunotherapy include: the type of effector cells, their state of activation, the type of effector receptor being activated or tareeted. the presence of Tregs, the affinity of the anti-effector cell antibody and the anti-TAA antibody, the type of BiAb (mouse, humanized, or human), the number of binding sites for the T cells or TAA, the presence or absence of decoy antigen, whether the TAA modulates after being engaged by antibody, the type of tumor, the tumor burden, and last, but not least, the amount of 'immunologic' space available for the adoptively transferred cells to expand and function.