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Adoptive transfer with high-affinity TCR to treat human solid tumors: how to improve the feasibility?

Abstract : The adoptive transfer of tumor antigen-specific T cells recently achieved clinical efficacy for a fraction of melanoma patients refractory to other therapies. Unfortunately , the application of this strategy to the remaining melanoma and most other cancer patients is hampered by the difficulty to generate high-affinity tumor-reactive T cells. Two strategies are currently developed to extend the feasibility of this therapeutic approach: clinical grade tool production for MHC-peptide multimer-driven sorting of antigen-specific T cells from the endogenous peripheral T cell repertoire and de novo engineering of the missing repertoire by genetic transfer of cloned specific T cell receptor (TCR) into T cells. The expected multiplication of adoptive transfer treatments, by these strategies, and their careful evaluation should enable the cure of a number of otherwise compromised cancer patients and to gain insight into the characteristics of transferred T cells best fitted to eradicate tumor cells, in terms of antigen specificities, phenotype, and functions. In particular, identification of tumor-rejection antigens by this approach would improve the design and efficacy of all immuno-therapeutic approaches.
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Submitted on : Tuesday, February 18, 2020 - 6:20:25 PM
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Francine Jotereau, Nadine Gervois, Nathalie Labarrière. Adoptive transfer with high-affinity TCR to treat human solid tumors: how to improve the feasibility?. Targeted Oncology, Springer Verlag (Germany), 2012, 7 (1), pp.3-14. ⟨10.1007/s11523-012-0207-z⟩. ⟨inserm-02483714⟩



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