Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Melanoma: A Systematic Review of Phase One Clinical Trials.

Abstract / Summary

IntroductionMelanoma is a growing health concern, with global incidence increasing annually. However, treatment for refractory disease is currently limited. Chimeric antigen receptor (CAR) T-cell therapy has shown promising results in haematological malignancies. Despite this, its utility in solid cancers, such as melanoma, is not yet established. We performed a systematic review of phase one trials to help determine and describe foundational understandings of the safety and efficacy of CAR T-cell therapy for melanoma.MethodsThis systematic review was conducted in accordance with the Cochrane Collaboration Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement Guidelines. Databases were searched to identify articles before November 18, 2025, which described the use of CAR T-cell therapy in melanoma patients with published results. Study, patient, and treatment characteristics were summarised and analysed.ResultsIn total, 2726 articles were screened. Ultimately 5 studies comprising 15 patients with melanoma treated with CAR T-cell therapy were analysed and discussed. T-cell therapies were all autologous and the targets for the CAR T-cell therapies included GD2, PD-1 and cMET antigens across a wide variety of cell doses. Across pooled data, clinical responses varied, with some patients displaying either a partial or complete clinical response. Treatment related effects were of grade one or two severity, with no serious adverse effects reported, including neurotoxicity side effects, or treatment limited related toxicity/mortality events. Peak expansion typically occurred within day 7 to 28, but persistence was limited across studies.ConclusionCAR T-cell therapy for melanoma is a novel treatment approach in its infancy. Results are preliminary, and remain largely descriptive, as findings are limited by heterogeneity and small sample sizes. Further investigation through additional phase one trials, and subsequent phase two/three trials, are required for better establishing direct clinical viability.

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