Emerging Immunotherapy Approaches for Treating Prostate Cancer

Abstract

Immunotherapy has emerged as an important approach for cancer treatment, but its clinical efficacy has been limited in prostate cancer compared to other malignancies. This review summarizes key immunotherapy strategies under evaluation for prostate cancer, including immune checkpoint inhibitors, bispecific T cell-engaging antibodies, chimeric antigen receptor (CAR) T cells, therapeutic vaccines, and cytokines. For each modality, the rationale stemming from preclinical studies is discussed along with outcomes from completed clinical trials and strategies to improve clinical efficacy that are being tested in ongoing clinical trials. Imperative endeavors include biomarker discovery for patient selection, deciphering resistance mechanisms, refining cellular therapies such as CAR T cells, and early-stage intervention were reviewed. These ongoing efforts instill optimism that immunotherapy may eventually deliver significant clinical benefits and expand treatment options for patients with advanced prostate cancer.

New approaches and prospects of immunotherapy and gene therapy for prostate cancer

“…All of these data suggested antitumor activity. In comparison to the 3 mg/kg dose used in melanoma, more treatment-related grade 3 to 4 adverse events (TRAEs) were reported (40% vs. 23%), and there were 9 treatment-related deaths [246,251] (Table 1 Completed Immune checkpoint inhibitors Phase 3 clinical trials in prostate cancer [251][252][253][254][255][256][257][258] ). Median OS with Pembrolizumab + Docetaxel was 19.6 months (95%CI: 18.2 to 20.9) compared to 19.0 months (95%CI: 17.9 to 20.9) with Docetaxel alone.…”

“…Primary endpoints were not met [257,258] . In the KEYNOTE-028 phase Ib study, pembrolizumab showed a 17.4% objective response rate (ORR) in 23 heavily treated mCRPC patients with measurable disease and ≥ 1% PD-L1 expression.…”

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer: Identification, prognosis and survival, genetic and epigenetic factors

“…Prostate cancers are often resistant to immunotherapies. There are running research trials to approach immunotherapy for PCa, CRPC, and t-NEPC[ 24 ].…”

Special Issue: “Novel Researches and Perspectives on Prostate Cancer”

“…An overview of the emerging immunotherapy approaches is given by Meng and co-workers [8]. In contrast to highly immunogenic malignancies, the immunosuppressive properties characterizing the microenvironment of PCa promote immune evasion, and this peculiarity has delayed the use of immunotherapy in the treatment of this disease [14].…”