Document Type
Article
Publication Date
4-15-2025
Abstract
Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor prior to treatment is associated with improved overall survival and tumor reduction on tebentafusp, that T cell recruitment occurs even in tumors with a low baseline level of T cell infiltration, and that durability of changes induced in the tumor microenvironment is key for survival duration.
Recommended Citation
Sacco, Joseph; Kirk, Peter; Leach, Emma; Shoushtari, Alexander; Carvajal, Richard; Britton-Rivet, Camille; Khakoo, Sophie; Collins, Laura; de la Cruz-Merino, Luis; Eroglu, Zeynep; Ikeguchi, Alexandra; Nathan, Paul; Hamid, Omid; Butler, Marcus; Stanhope, Sarah; Ranade, Koustubh; and Sato, Takami, "Evolution of the Tumor Immune Landscape During Treatment With Tebentafusp, a T Cell Receptor-CD3 Bispecific" (2025). Department of Medical Oncology Faculty Papers. Paper 292.
https://jdc.jefferson.edu/medoncfp/292
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Table S4. Anatomical site of biopsies analyzed by RNA-seq, related to Table 1 and Figure 2.csv (2 kB)
Table S5. Gene expression at baseline, related to Figure 2.csv (77 kB)
Table S6. Gene expression on-treatment, related to Figure 4.csv (38 kB)
Table S7. Gene expression at progression, related to Figure 6.csv (2 kB)
Table S8. Patient metadata, related to Figures 1 and 2 and Table 1.csv (11 kB)
Document S2. Article plus supplemental information.pdf (9565 kB)
PubMed ID
40239619
Language
English
Included in
Amino Acids, Peptides, and Proteins Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Immunotherapy Commons, Neoplasms Commons, Oncology Commons
Comments
This article is the author's final published version in Cell Reports Medicine, Volume 6, Issue 4, April 2025, Article number 102076.
The published version is available at https://doi.org/10.1016/j.xcrm.2025.102076.
Copyright © 2025 The Authors