Current Developments in Cellular Therapy for Castration Resistant Prostate Cancer: A Systematic Review of Clinical Studies

Abstract

Recently, the development of immunotherapies such as cellular therapy, monoclonal antibodies, vaccines and immunomodulators has revolutionized the treatment of various cancer entities. In order to close the existing gaps in knowledge about cellular immunotherapy, specifically focusing on the chimeric antigen receptors (CAR) T-cells, their benefits and application in clinical settings, we conducted a comprehensive systematic review. Two co-authors independently searched the literature and characterized the results. Out of 183 records, 26 were considered eligible. This review provides an overview of the cellular immunotherapy landscape in treating prostate cancer, honing in on the challenges of employing CAR T-cell therapy. CAR T-cell therapy is a promising avenue for research due to the presence of an array of different tumor specific antigens. In prostate cancer, the complex microenvironment of the tumor vastly contributes to the success or failure of immunotherapies.

Keywords: CAR-T; cellular therapy; dendritic cells; immunotherapy; mCRPC; vaccines.

Figure 1

Generations of CAR-T Cells. (a) 1st Generation CAR-Ts; (b) 2nd Generation consisting of an extra costimulatory domain; (c) 3rd Generation CAR-Ts with a second costimulatory receptor; (d) 4th Generation CAR-Ts—“next generation” with an addition of proinflammatory cytokines and costimulatory elements (knock-in/knock out genes) [30]. Figures originally created by C.S.

Figure 2

Methodology of literature search according to PRISMA guidelines. Figures originally created by C.S.