PERSPECTIVE article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCommunity Series in Novel Preclinical Model, Biomarker, Treatment and Drug Delivery to Address Immune Evasion in Cancer: Volume IIView all 6 articles
Melanoma Vaccines: Current R&D Landscape, Translational Hurdles, and Future Outlook—A Perspective Drawn from 442 Clinical Trials
Provisionally accepted
- The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Background: Melanoma is a highly malignant skin tumor with high metastasis risk and poor advanced-stage survival, posing a global public health challenge due to conventional treatment limitations. Tumor immunotherapy, especially cancer vaccines, offers promise by activating/regulating immune responses against cancer cells. Methods: Following PRISMA guidelines, we systematically searched the Trialtrove database for interventional melanoma cancer vaccine trials up to August 5, 2025. After dual independent screening, 442 trials were analyzed for reliability. Results: Trials were geographically concentrated (69% in the US) with minimal participation from Asia, Africa, and Latin America. A "translational funnel effect" emerged: 63.6% were Phase I/I-II, only 6.1% Phase III, with a 22.9% termination rate. Peptide/recombinant protein (186 trials) and cellular vaccines (151 trials) were mainstream, with nucleic acid vaccines (58 trials) emerging. Combination therapy (>50%, 227 trials), mostly with immune checkpoint inhibitors (ICIs), dominated; adjuvants enhanced efficacy. 91.1% focused on Stage III/IV patients: key trials showed mRNA-4157 + pembrolizumab reduced recurrence/death risk by 49% in resected melanoma, and herpes simplex virus RP1 + nivolumab achieved 58.3% objective response rate (ORR) in ICI-resistant patients. Primary endpoints favored safety (215 trials) and immunogenicity (142 trials), with overall survival rarely used (33 trials); academic institutions led funding (52.3%). Conclusions: Melanoma vaccines, particularly personalized platforms combined with ICIs, have significant potential. However, challenges include tumor heterogeneity, immunosuppressive tumor microenvironment (TME), inefficient delivery, geographical R&D imbalance, and low Phase III conversion. Interdisciplinary collaboration, international multicenter trials, optimized clinical design (e.g., early-stage enrollment), and policy support are needed to advance clinical translation.
Keywords: Melanoma, cancer vaccine, clinical trials, combination therapy, Immunotherapy
Received: 03 Sep 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Gao, Duan, Peng, Zhao, Li and Mou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kuanhou Mou
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