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Pinpointing the tumor-specific T cells via TCR clusters.
Goncharov, Mikhail M; Bryushkova, Ekaterina A; Sharaev, Nikita I; Skatova, Valeria D; Baryshnikova, Anastasiya M; Sharonov, George V; Karnaukhov, Vadim; Vakhitova, Maria T; Samoylenko, Igor V; Demidov, Lev V; Lukyanov, Sergey; Chudakov, Dmitriy M; Serebrovskaya, Ekaterina O.
Afiliación
  • Goncharov MM; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation.
  • Bryushkova EA; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
  • Sharaev NI; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
  • Skatova VD; Department of Molecular Biology, Moscow State University, Moscow, Russian Federation.
  • Baryshnikova AM; Pirogov Russian National Research Medical University, Moscow, Russian Federation.
  • Sharonov GV; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation.
  • Karnaukhov V; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
  • Vakhitova MT; Pirogov Russian National Research Medical University, Moscow, Russian Federation.
  • Samoylenko IV; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
  • Demidov LV; Pirogov Russian National Research Medical University, Moscow, Russian Federation.
  • Lukyanov S; Pirogov Russian National Research Medical University, Moscow, Russian Federation.
  • Chudakov DM; Laboratory of Genomics of Antitumor Adaptive Immunity, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation.
  • Serebrovskaya EO; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation.
Elife ; 112022 04 04.
Article en En | MEDLINE | ID: mdl-35377314
Adoptive 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 lysed 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Neoplasias Límite: Humans Idioma: En Revista: Elife Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Neoplasias Límite: Humans Idioma: En Revista: Elife Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido