Abstract
Simple SummaryTechnical advances in immunotherapies have led to the development of novel T cell receptor (TCR)-based approaches to fight cancer. One of these therapies, tebentafusp, has shown a significant benefit in the overall survival of uveal melanoma patients for the first time. This review focuses on TCR-directed therapies in the treatment of uveal melanoma.Metastatic uveal melanoma (mUM) is one of the most rapidly progressing tumors, with a bad prognosis and no standard-of-care treatment. Immune checkpoint inhibitors have revolutionized cancer therapy and improved overall survival in patients with metastatic cutaneous melanoma (mCM). However, this approach has been largely unimpressive, with no significant impact on the survival of mUM patients. Technical advances in immunotherapies have led to the development of novel T cell receptor (TCR)-based approaches to fight cancer. For the first time in over 50 years, compelling evidence demonstrates the power of TCR-based approaches for survival in mUM patients. Hence, this review summarizes novel TCR-based immunotherapeutic strategies currently in clinical studies for mUM treatment. We also discuss the potential combinational treatments to these strategies to maximize the clinical benefits.
Highlights
Uveal melanoma (UM) is a rare yet very aggressive tumor arising from melanocytes located in the eye
We provide a summary of novel T cell receptor (TCR)-based immunotherapeutic strategies, including TCR cell-based (TIL therapy, TCR-engineered T cells) and non-cell-based therapies (ImmTACs) in clinical and preclinical studies for uveal melanoma (Table 1)
The extensively laborious process involved in the development of cell-based TCR therapies limits their global accessibility
Summary
Uveal melanoma (UM) is a rare yet very aggressive tumor arising from melanocytes located in the eye. The lower expressions of PD1 and PDL1 suggest that there is either a lack of tumor-specific immune infiltration or that they are suppressed in the TME by other means [16–18] These data suggest that immunotherapies that reverse the exhaustion of existing immune cells but rather drive tumor-specific immune cells to the TME may provide a clinical benefit in mUM patients. As HLA molecules present both intra- and extracellular tumor proteins, TCRs can be engineered to identify and target tumor antigens that were previously less targetable, suggesting the potential of TCR-based therapies for targeting non-immunogenic cancers such as UM. Tebentafusp (IMCgp100) versus investigator choice (dacarbazine, ipilimumab, or pembrolizumab) in mUM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
