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Cancer Cell International
Published in: Cancer Cell International 1/2024

Open Access 01-12-2024 | Esophageal Cancer | Research

NY-ESO-1-specific T cell receptor-engineered T cells and Tranilast, a TRPV2 antagonist bivalent treatment enhances the killing of esophageal cancer: a dual-targeted cancer therapeutic route

Authors: Obed Boadi Amissah, Wenfang Chen, Jean de Dieu Habimana, Yirong Sun, Lihui Lin, Yujie Liu, Ling Wang, Zhaoming Liu, Omar Mukama, Rajesh Basnet, Hohua Liu, Junyi Li, Xuanyan Ding, Lingshuang Lv, Min Chen, Yalin Liang, Rongqi Huang, Zhiyuan Li

Published in: Cancer Cell International | Issue 1/2024

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Abstract

Background

Esophageal cancer (EC) is a global canker notorious for causing high mortality due to its relentless incidence rate, convoluted with unyielding recurrence and metastasis. However, these intricacies of EC are associated with an immoderate expression of NY-ESO-1 antigen, presenting a lifeline for adoptive T cell therapy. We hypothesized that naturally isolated higher-affinity T cell receptors (TCRs) that bind to NY-ESO-1 would allow T lymphocytes to target EC with a pronounced antitumor response efficacy. Also, targeting TRPV2, which is associated with tumorigenesis in EC, creates an avenue for dual-targeted therapy. We exploited the dual-targeting antitumor efficacy against EC.

Methods

We isolated antigen-specific TCRs (asTCRs) from a naive library constructed with TCRs obtained from enriched cytotoxic T lymphocytes. The robustness of our asTCRs and their TCR-T cell derivatives, Tranilast (TRPV2 inhibitor), and their bivalent treatment were evaluated with prospective cross-reactive human-peptide variants and tumor cells.

Results

Our study demonstrated that our naive unenhanced asTCRs and their TCR-Ts perpetuated their cognate HLA-A*02:01/NY-ESO-1(157–165) specificity, killing varying EC cells with higher cytotoxicity compared to the known affinity-enhanced TCR (TCRe) and its wild-type (TCR0) which targets the same NY-ESO-1 antigen. Furthermore, the TCR-Ts and Tranilast bivalent treatment showed superior EC killing compared to any of their monovalent treatments of either TCR-T or Tranilast.

Conclusion

Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.
Appendix
Available only for authorised users
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Metadata
Title
NY-ESO-1-specific T cell receptor-engineered T cells and Tranilast, a TRPV2 antagonist bivalent treatment enhances the killing of esophageal cancer: a dual-targeted cancer therapeutic route
Authors
Obed Boadi Amissah
Wenfang Chen
Jean de Dieu Habimana
Yirong Sun
Lihui Lin
Yujie Liu
Ling Wang
Zhaoming Liu
Omar Mukama
Rajesh Basnet
Hohua Liu
Junyi Li
Xuanyan Ding
Lingshuang Lv
Min Chen
Yalin Liang
Rongqi Huang
Zhiyuan Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-024-03249-w

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