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Updated: Jul 26, 2025
Retroviral Transduction of T-cell Receptors in Mouse T-cells
Published on: October 22, 2010
Unique features of the TCR repertoire of reactivated memory T cells in the experimental mouse tumor model
Anastasiia Kalinina1, Nadezda Persiyantseva1, Olga Britanova2,3
1N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Kashirskoe sh. 24, 115478 Moscow, Russian Federation.
Abstract:
T cell engineering with T cell receptors (TCR) specific to tumor antigens has become a breakthrough towards personalized cancer adoptive cell immunotherapy. However, the search for therapeutic TCRs is often challenging, and effective strategies are strongly required for the identification and enrichment of tumor-specific T cells that express TCRs with superior functional characteristics. Using an experimental mouse tumor model, we studied sequential changes in TCR repertoire features of T cells involved in the primary and secondary immune responses to allogeneic tumor antigens. In-depth bioinformatics analysis of TCR repertoires showed differences in reactivated memory T cells compared to primarily activated effectors. After cognate antigen re-encounter, memory cells were enriched with clonotypes that express α-chain TCR with high potential cross-reactivity and enhanced strength of interaction with both MHC and docked peptides. Our findings suggest that functionally true memory T cells could be a better source of therapeutic TCRs for adoptive cell therapy. No marked changes were observed in the physicochemical characteristics of TCRβ in reactivated memory clonotypes, indicative of the dominant role of TCRα in the secondary allogeneic immune response. The results of this study could further contribute to the development of TCR-modified T cell products based on the phenomenon of TCR chain centricity.
Insights
Memory T cells, crucial for adoptive cell therapy, possess tumor-specific T cell receptors (TCRs) with enhanced cross-reactivity. This study highlights memory T cells as a superior source for therapeutic TCRs in cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Research
- Biotechnology
Background:
- T cell receptor (TCR) engineering is vital for personalized cancer immunotherapy.
- Identifying potent tumor-specific TCRs for adoptive cell therapy remains a challenge.
- Understanding T cell memory responses is key to improving therapeutic strategies.
Purpose of the Study:
- To investigate TCR repertoire dynamics during primary and secondary immune responses to tumor antigens.
- To identify features of T cells that make them suitable for adoptive cell therapy.
- To explore the role of TCR alpha and beta chains in secondary immune responses.
Main Methods:
- Utilized a mouse tumor model to study T cell responses.
- Performed in-depth bioinformatics analysis of T cell receptor repertoires.
- Analyzed sequential changes in T cell populations during primary and secondary immune responses.
Main Results:
- Reactivated memory T cells exhibited distinct TCR repertoire features compared to primary effector T cells.
- Memory T cells were enriched with T cell receptor (TCR) clonotypes expressing alpha chains with high cross-reactivity and binding affinity.
- TCR alpha chain characteristics, not TCR beta, dominated the secondary allogeneic immune response.
Conclusions:
- Functionally true memory T cells represent a promising source for therapeutic TCRs in adoptive cell therapy.
- The dominant role of the TCR alpha chain in secondary responses offers insights for TCR engineering.
- Findings support the development of TCR-engineered T cell therapies based on TCR chain centricity.
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