Effectiveness of chimeric antigen receptor-T therapy on prostate cancer: A preclinical and clinical systematic review

Abstract

Chimeric antigen receptor-T (CAR-T) therapy has been an effective treatment for leukemia and lymphoma. Unlike hematological cancers, solid tumors like prostate cancer utilize a dynamic microenvironment to evade the host immune defenses. We aimed to systematically review preclinical and clinical studies to evaluate how CAR-T therapies in prostate cancer modify the tumor microenvironment and influence patient outcomes. PubMed, Embase, and Scopus were screened for published, peer reviewed preclinical and clinical studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The CAR-T antigen, tumor eradication rates, change in prostate-specific antigen (PSA) expression, and tumor tissue infiltration were compared across studies. Nineteen preclinical trials examining xenograft mice models and 3 phase I clinical trials with 32 total patients were included in this review. Tumor eradication rates in mice treated with armored CAR-T therapy were significantly greater than that of mice treated with unarmored CAR-T cells (p-value <.05). Ten of 32 clinical trial patients had a minimum of 30% PSA decline. Patients receiving higher doses of lymphocyte depletion (LD) therapy had higher peaks of CAR-T expansion, and those receiving LD therapy before CAR-T infusion experienced reduced dose-limiting toxicities. Immunohistochemistry staining of biopsied tumor tissue suggests CAR-T increased T cell proliferation markers and upregulated cytokines. CAR-T cells can modify the tumor microenvironment when armored or paired with LD therapy. Future studies should include expanded clinical investigations, particularly using armored CAR-T cells with LD regimens, to determine its safety and efficacy profiles in prostate cancer.

Keywords

Chimeric antigen receptor-T / Chimeric antigen receptor-T therapy / Prostate cancer / Solid tumors

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