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Updated: Oct 24, 2025

A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
The Promise of Personalized TCR-Based Cellular Immunotherapy for Cancer Patients
Marion Arnaud1,2, Sara Bobisse1,2, Johanna Chiffelle1,2
1Department of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
Abstract:
Mutation-derived neoantigens are now established as attractive targets for cancer immunotherapy. The field of adoptive T cell transfer (ACT) therapy was significantly reshaped by tumor neoantigens and is now moving towards the genetic engineering of T cells with neoantigen-specific T cell receptors (TCRs). Yet, the identification of neoantigen-reactive TCRs remains challenging and the process needs to be adapted to clinical timelines. In addition, the state of recipient T cells for TCR transduction is critical and can affect TCR-ACT efficacy. Here we provide an overview of the main strategies for TCR-engineering, describe the selection and expansion of optimal carrier cells for TCR-ACT and discuss the next-generation methods for rapid identification of relevant TCR candidates for gene transfer therapy.
Insights
Identifying neoantigen-reactive T cell receptors (TCRs) for adoptive T cell transfer (ACT) therapy is challenging. This review covers TCR engineering strategies, carrier cell selection, and rapid TCR identification methods for improved cancer immunotherapy.
Area of Science:
- * Oncology
- * Immunology
- * Genetic Engineering
Background:
- * Mutation-derived neoantigens are key targets in cancer immunotherapy.
- * Adoptive T cell transfer (ACT) therapy is advancing with neoantigen-specific T cell receptors (TCRs).
- * Current methods for identifying neoantigen-reactive TCRs face challenges with clinical timelines.
Purpose of the Study:
- * To provide an overview of T cell receptor (TCR) engineering strategies.
- * To describe the selection and expansion of carrier cells for TCR-ACT.
- * To discuss next-generation methods for rapid identification of TCR candidates for gene therapy.
Main Methods:
- * Review of current TCR engineering techniques.
- * Analysis of carrier cell selection and expansion protocols for ACT.
- * Exploration of emerging technologies for TCR candidate identification.
Main Results:
- * TCR engineering is central to advancing ACT.
- * Optimal carrier cell selection is crucial for ACT efficacy.
- * Rapid identification of TCR candidates is essential for clinical translation.
Conclusions:
- * Advances in TCR engineering and carrier cell selection are critical for effective ACT.
- * Novel methods are needed to accelerate the identification of neoantigen-reactive TCRs.
- * Streamlining TCR identification and gene transfer holds promise for personalized cancer immunotherapy.
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