Pinpointing the tumor-specific T-cells via TCR clusters

Goncharov, M.; Bryushkova, E. A.; Sharayev, N. I.; Skatova, V. D.; Baryshnikova, A. M.; Sharonov, G. V.; Samoylenko, I. V.; Demidov, L. V.; Chudakov, D. M.; Serebrovskaya, E. O.

doi:10.1101/2022.01.30.478375

bioRxiv · 10.1101/2022.01.30.478375

Pinpointing the tumor-specific T-cells via TCR clusters

Goncharov, M.·Bryushkova, E. A.·Sharayev, N. I.·Skatova, V. D.·Baryshnikova, A. M.·Sharonov, G. V.·Samoylenko, I. V.·Demidov, L. V.·Chudakov, D. M.·Serebrovskaya, E. O.

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Abstract

Adoptive T cell transfer (ACT) is a promising approach to cancer immunotherapy, but its efficiency fundamentally depends on the extent of tumor-specific T-cell enrichment within the graft. This can be estimated via activation with identifiable neoantigens, tumor-associated antigens (TAAs), or living or lyzed tumor cells, but these approaches remain laborious, time-consuming, and functionally limited, hampering clinical development of ACT. Here, we demonstrate that homology cluster analysis of T cell receptor (TCR) repertoires efficiently identifies tumor-reactive TCRs allowing to: 1) detect their presence within the pool of tumor-infiltrating lymphocytes (TILs); 2) optimize TIL culturing conditions, with IL-2low/IL-21/anti-PD-1 combination showing increased efficiency; 3) investigate surface marker-based enrichment for tumor-targeting T cells in freshly-isolated TILs (enrichment confirmed for CD4+ and CD8+ PD-1+/CD39+ subsets), or re-stimulated TILs (informs on enrichment in 4-1BB-sorted cells). We believe that this approach to the rapid assessment of tumor-specific TCR enrichment should accelerate T cell therapy development.

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Goncharov, M., Bryushkova, E. A., Sharayev, N. I., Skatova, V. D., Baryshnikova, A. M., Sharonov, G. V., Samoylenko, I. V., Demidov, L. V., Chudakov, D. M., Serebrovskaya, E. O.. 2022-01-30. Pinpointing the tumor-specific T-cells via TCR clusters. https://doi.org/10.1101/2022.01.30.478375

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