Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives.

Abstract

Simple SummaryDespite recent advances in treatment, metastasized prostate carcinoma (PC) still has a poor prognosis. Immunotherapy has revolutionized the landscape of cancer therapy, but a breakthrough for PC is missing. The success of immunotherapy in cancers is mostly due to recent strategies to mobilize T cells comprising immune checkpoint inhibition, CAR-T cells and bispecific antibodies (bsAbs). After introducing present approaches and immunotherapy in PC in general, we here review the current clinical development of bsAbs in PC treatment.Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an “off the shelf” reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives.