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Volume 14
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Review

Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy

by
Apoorva Mehta
1,*,
Mateen Motavaf
2,
Ikenna Nebo
1,
Sophia Luyten
1,
Kofi D. Osei-Opare
1 and
Alejandro A. Gru
3
1
Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA
2
Duke University School of Medicine, Durham, NC 27710, USA
3
Department of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(4), 1200; https://doi.org/10.3390/jcm14041200
Submission received: 16 January 2025 / Revised: 8 February 2025 / Accepted: 11 February 2025 / Published: 12 February 2025
(This article belongs to the Section Dermatology)
Versions Notes

Abstract

Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), and tumor-infiltrating lymphocyte (TIL) therapies. PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma. T-VEC, a modified oncolytic herpes virus, promotes a systemic anti-tumor response while simultaneously lysing malignant cells. mRNA vaccines, such as Moderna’s mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue. TIL therapy is a form of therapy involving ex vivo expansion and reinfusion of the patient’s tumor-specific lymphocytes and has been shown to provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges such as tumor resistance, high financial burden, and limited accessibility pose challenges to their widespread use. This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events.
Keywords: melanoma; treatment; mRNA vaccine; TIL; therapy; T-VEC; PD-1 inhibitors; PD-L1 inhibitors; CAR-T; T-cell; immunotherapy; advancement melanoma; treatment; mRNA vaccine; TIL; therapy; T-VEC; PD-1 inhibitors; PD-L1 inhibitors; CAR-T; T-cell; immunotherapy; advancement

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MDPI and ACS Style

Mehta, A.; Motavaf, M.; Nebo, I.; Luyten, S.; Osei-Opare, K.D.; Gru, A.A. Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. J. Clin. Med. 2025, 14, 1200. https://doi.org/10.3390/jcm14041200

AMA Style

Mehta A, Motavaf M, Nebo I, Luyten S, Osei-Opare KD, Gru AA. Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. Journal of Clinical Medicine. 2025; 14(4):1200. https://doi.org/10.3390/jcm14041200

Chicago/Turabian Style

Mehta, Apoorva, Mateen Motavaf, Ikenna Nebo, Sophia Luyten, Kofi D. Osei-Opare, and Alejandro A. Gru. 2025. "Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy" Journal of Clinical Medicine 14, no. 4: 1200. https://doi.org/10.3390/jcm14041200

APA Style

Mehta, A., Motavaf, M., Nebo, I., Luyten, S., Osei-Opare, K. D., & Gru, A. A. (2025). Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. Journal of Clinical Medicine, 14(4), 1200. https://doi.org/10.3390/jcm14041200

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