CAR-T cell therapy: a potential new strategy against prostate cancer

Abstract

Prostate cancer (PCa) is one of the main causes of cancer-related death in men. In the present immunotherapy era, several immunotherapeutic agents have been evaluated in PCa with poor results, possibly due to its low mutational burden. The recent development of chimeric antigen receptor (CAR)-T cell therapy redirected against cancer-specific antigens would seem to provide the means for bypassing immune tolerance mechanisms. CAR-T cell therapy has proven effective in eradicating hematologic malignancies and the challenge now is to obtain the same degree of in solid tumors, including PCa. In this study we review the principles that have guided the engineering of CAR-T cells and the specific prostatic antigens identified as possible targets for immunological and non-immunological therapies. We also provide a state-of-the-art overview of CAR-T cell therapy in PCa, defining the key obstacles to its development and underlining the mechanisms used to overcome these barriers. At present, although there are still many unanswered questions regarding CAR-T cell therapy, there is no doubt that it has the potential to become an important treatment option for urological malignancies.

Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

“…In particular, these include cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, CD152), the programmed cell death 1 receptor (PD-1 also known as CD279), and ligand 1 and 2 of programmed cell death receptor (PD-L1 and PD-L2 also known as CD274 and CD273, respectively). These molecules appear on activated cytotoxic T lymphocytes and serve to regulate the immune response to prevent autoimmune damage [74,75]. An example of such a molecule is pembrolizumab, which blocks PD-1.…”

Electroporation-Based Treatments in Urology

“…However, it has to be emphasized that none of the further mentioned trials concerning CAR-T for urological malignancies applies electroporation for gene transfection. Generally, due to the high expression on the prostate gland tissue, PSMA and PSCA are utilized as the targets for the CAR-T cell therapy for prostate cancer [ 186 , 187 , 188 ]. High effectivity of the therapy led to the registration of CAR-T against PSMA for phase I clinical trials in patients with metastatic prostate cancer (NCT01140373).…”

Contribution of Macrophages and T Cells in Skeletal Metastasis

“…CAR-T cells could also be used for the treatment of carcinoma if the appropriate antigen is targeted. For prostate cancer, CARs binding to the prostate-specific membrane antigen (PSMA), the prostate stem cell antigen (PSCA), and EpCAM have been tested in preclinical and phase I clinical trials [344]. Antigens such as ErbB2, MUC1, cMet, or Mesothelin have been tested in mice and in phase I or II trials for the treatment of breast cancer [345].…”