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Open AccessReview
Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets
by
Mariana Grigoruta
Mariana Grigoruta 1,2
,
Xiaohua Kong
Xiaohua Kong 1 and
Yong Qin
Yong Qin 1,*
1
Department of Pharmaceutical Sciences, School of Pharmacy, The University of Texas at El Paso, El Paso, TX 79902, USA
2
Department of Health Sciences, Biomedical Sciences Institute, Autonomous University of Ciudad Juarez, Ciudad Juárez 32310, Mexico
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(14), 5137; https://doi.org/10.3390/jcm14145137 (registering DOI)
Submission received: 27 May 2025
/
Revised: 8 July 2025
/
Accepted: 15 July 2025
/
Published: 19 July 2025
Abstract
Uveal melanoma (UM), the most common primary intraocular malignancy in adults, poses a unique clinical challenge due to its high propensity for liver metastasis and poor responsiveness to conventional therapies. Despite the expanding landscape of immunotherapy in oncology, progress in managing metastatic uveal melanoma (mUM) remains limited, and no universally accepted standard of care has been established. In this review, we examine the current state and evolving strategies in immunotherapy for mUM, focusing on immune checkpoint inhibitors (ICIs), T cell receptor (TCR)-engineered therapies, and tumor-targeted vaccines. We also present a meta-analytical comparison of clinical outcomes between ICI monotherapy and combination regimens, alongside the recently FDA-approved T cell engager tebentafusp. Our analysis indicates that the triple combination of Ipilimumab, anti-PD-1 agents, and tebentafusp significantly enhances objective response rates, disease control rates, 1-year overall survival rates, and median overall survival (mOS) compared to ICI monotherapy alone. However, this enhanced efficacy is accompanied by increased toxicity due to broader immune activation. In contrast, tebentafusp offers superior tumor specificity and a more favorable safety profile in HLA-A*02:01-positive patients, positioning it as a preferred therapeutic option for this genetically defined subset of UM. Additionally, early-phase studies involving dendritic cell-based immunotherapies and peptide vaccines has shown encouraging signs of tumor-specific immune activation, along with improved tolerability. Collectively, this review underscores the urgent need for more precise and effective immunotherapeutic approaches tailored to the unique biology of mUM.
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MDPI and ACS Style
Grigoruta, M.; Kong, X.; Qin, Y.
Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets. J. Clin. Med. 2025, 14, 5137.
https://doi.org/10.3390/jcm14145137
AMA Style
Grigoruta M, Kong X, Qin Y.
Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets. Journal of Clinical Medicine. 2025; 14(14):5137.
https://doi.org/10.3390/jcm14145137
Chicago/Turabian Style
Grigoruta, Mariana, Xiaohua Kong, and Yong Qin.
2025. "Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets" Journal of Clinical Medicine 14, no. 14: 5137.
https://doi.org/10.3390/jcm14145137
APA Style
Grigoruta, M., Kong, X., & Qin, Y.
(2025). Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets. Journal of Clinical Medicine, 14(14), 5137.
https://doi.org/10.3390/jcm14145137
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