ArticleJournal of translational medicine2025
MUC18-Directed chimeric antigen receptor T cells for the treatment of mucosal melanoma.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Preclinical and Virtual Models of Mucosal Melanoma: Bridging Translational Gaps in a Rare and Lethal Cancer.Pigment cell & melanoma research · 2026Review
- Rare primary anorectal malignant melanoma presenting with painless hematochezia: a case report.Frontiers in oncology · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
purposeMucosal melanoma, a highly aggressive form of skin cancer, remains challenging to manage due to the lack of effective therapies. Mucin 18 (MUC18) is overexpressed in both primary and metastatic lesions of melanoma but rarely in normal tissues. The expression profile makes MUC18 a potential target for development of therapeutic antibodies or chimeric antigen receptor-T (CAR-T) cell therapy. This study aims to generate an effective CAR-T targeting MUC18-positive melanoma and evaluate its preclinical antitumor activity. EXPERIMENTAL
designA humanized anti-MUC18 single chain antibody fragment (scFv) was used to construct CAR-T with various designs of the hinge, transmembrane, co-stimulatory, and CD3ζ domains. The antitumor efficacy of MUC18 CAR-T cells was assessed in vitro, in MUC18-positive primary and rechallenged xenograft models, as well as in patient-derived xenograft (PDX) models of human mucosal melanoma.
resultsThe humanized scFv selectively bound to MUC18 with high affinity. Various MUC18 CAR-T cells specifically killed MUC18-positive melanoma cells and could proliferate as a result of exposure to antigen. Among them, CAR-T cells containing an IgG4-derived hinge domain and a CD28 co-stimulatory domain demonstrated superior antitumor efficiency. Robust tumor regression and CAR-T cell expansion were observed in multiple MUC18-positive xenograft models after treatment with the IgG4 hinge and CD28 empowered CAR-T cells.
conclusionsThis study demonstrated the development of a novel CAR-T therapy for mucosal melanoma, MUC18 CAR-T, that showed strong potency in tumor eradication and inhibition of tumor relapse. This candidate CAR-T therapy could provide a promising strategy for the treatment of the refractory melanoma.
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