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Updated: Sep 27, 2025
A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Novel chimeric antigen receptor T cells based on T-cell receptor-like antibodies
1Institute of Translational Medicine, Cancer Centre, Biological Imaging & Stem Cell Core, Faculty of Health Sciences, University of Macau, Taipa, Macau SPR, China.
Abstract:
The need for novel therapeutics against human cancers such as leukemias and solid tumors is well recognized. Human T cells are poised to make a fundamental change in the therapeutic approach. T-cell interaction with a tumor cell is a critical event and primarily driven by T-cell receptor (TCR) recognition of peptide in the pocket HLA. However, among TCR-based T-cell therapies, either TCR mismatching or the low density of major histocompatibility complex causes tumor cells to escape from the immune response. TCR molecules have low binding affinities, preventing their recognitions. Undoubtedly, antibody therapeutics is an effective treatment for cancer. As the new generation of monoclonal antibodies, TCR-like antibodies can mimic TCR recognition but are not susceptible for mechanisms of tumor evasion from the immune response. As chimeric antigen receptor (CAR) structure expressed on the surface of T cells, TCR-like antibodies can confer antigen specificity to T cells. The new TCR-like CAR may be important to drive new technologies of adoptive cell therapy, in particular, T-cell therapy, and open possibilities to target endogenous tumor-specific antigens.
Insights
Novel TCR-like antibodies offer a new approach to cancer therapy by enhancing T-cell specificity and overcoming tumor evasion mechanisms. This breakthrough promises improved adoptive cell therapy for leukemias and solid tumors.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Human T cells are crucial for anti-cancer immunity, primarily through T-cell receptor (TCR) recognition of tumor antigens presented by HLA molecules.
- Current TCR-based therapies face challenges like TCR mismatching and low HLA density, leading to tumor immune escape.
- TCRs exhibit low binding affinities, limiting their therapeutic efficacy against cancer cells.
Purpose of the Study:
- To introduce TCR-like antibodies as a novel therapeutic strategy for cancer treatment.
- To highlight the potential of TCR-like antibodies in overcoming common tumor evasion mechanisms.
- To explore the application of TCR-like antibodies in developing advanced adoptive T-cell therapies.
Main Methods:
- Development of TCR-like antibodies designed to mimic TCR recognition of tumor antigens.
- Engineering of chimeric antigen receptors (CARs) incorporating TCR-like antibodies to enhance T-cell targeting.
- Investigation of TCR-like CARs for improved antigen specificity and reduced susceptibility to tumor immune evasion.
Main Results:
- TCR-like antibodies demonstrate the ability to recognize tumor antigens similarly to TCRs.
- These antibodies are not susceptible to typical tumor evasion strategies that affect natural TCR interactions.
- TCR-like antibodies, when integrated into CARs, confer specific antigen recognition to T cells.
Conclusions:
- TCR-like antibodies represent a promising new generation of cancer therapeutics.
- TCR-like CARs can significantly advance adoptive T-cell therapy by enabling targeted recognition of endogenous tumor antigens.
- This approach holds potential for treating various cancers, including leukemias and solid tumors.
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