Cancer Vaccine Targeting Mutated GNAQ-Expressing Uveal Melanoma

Authors

Vitali Alexeev, Thomas Jefferson UniversityFollow
Mizue Terai, Thomas Jefferson UniversityFollow
Sergei Koshkin, Thomas Jefferson UniversityFollow
Olga Igoucheva, Thomas Jefferson UniversityFollow
Takami Sato, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

1-31-2026

Comments

This article is the author’s final published version in Cancers, Volume 18, Issue 3, 2026, Article number 480.

The published version is available at https://doi.org/10.3390/cancers18030480. Copyright © 2026 by the authors.

Abstract

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver mutation in GNAQ and GNA11 G-alpha proteins. Methods: Several DNA constructs encoding mutated GNAQ were developed and tested for activation of UM-reactive T cells in HLA-A2/Hd transgenic mice and human T cells ex vivo. Results: Constructs containing immune-enhancing PADRE and VP22-derived epitopes boosted T cell responses against mutant GNAQ, which correlated with reduced experimental lung metastases. Ex vivo dendritic cell-mediated T cell activation with vaccine constructs containing optimized structure produced cytolytic T cells that secreted IFN gamma and killed mutated GNAQ-expressing UM cells in vitro. Conclusions: These findings propose the utility of the fusion DNA vaccines in eliciting T cell immunity against UM cells bearing the Q209L mutation in GNAQ/GNA11 protein to prevent the establishment and progression of metastatic disease.

Recommended Citation

Alexeev, Vitali; Terai, Mizue; Koshkin, Sergei; Igoucheva, Olga; and Sato, Takami, "Cancer Vaccine Targeting Mutated GNAQ-Expressing Uveal Melanoma" (2026). Department of Medical Oncology Faculty Papers. Paper 328.
https://jdc.jefferson.edu/medoncfp/328

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

41681951

Language

English