Bispecific T-Cell Engagers Therapies in Solid Tumors: Focusing on Prostate Cancer

SIMPLE SUMMARY: Cancer treatments have significantly changed with the introduction of immunotherapy. Recently, the development of new agents that harness the redirection of T-cells against cancer is rapidly emerging in multiple tumor types. Since bispecific T-cell engager (BiTE) therapies have demonstrated clinical benefit in hematologic malignancies, their application to solid tumors has been an active area of investigation. However, in prostate cancer, due to the heterogeneous and immune-suppressive tumor microenvironment, the development of immunotherapy strategies remains a therapeutic challenge. In this review, we summarize the current development of BiTE therapies in solid tumors with a particular focus on clinical trials in advanced prostate cancer. ABSTRACT: Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research.