Identification of clinically relevant t cell receptors for personalized t cell therapy using combinatorial algorithms

Article Article scientifique Article Identification of clinically relevant t cell receptors for personalized t cell therapy using combinatorial algorithms eng 2024-05-07 author Pétremand Rémy 0000-0002-7629-7336 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Chiffelle Johanna 0000-0002-8312-2681 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Bobisse Sara Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Perez Marta A S Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Molecular Modelling Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. author Schmidt Julien Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.,Center of Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Arnaud Marion 0000-0003-0534-2379 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Barras David 0000-0001-8985-4704 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. 927944 author Lozano-Rabella Maria 0000-0002-6304-3919 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Genolet Raphaël 0000-0001-9335-3945 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. 631340 author Sauvage Christophe Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Saugy Damien Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Michel Alexandra Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Huguenin-Bergenat Anne-Laure Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Capt Charlotte Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Moore Jonathan 0000-0002-7586-671X Department of Medicine and Center of Translational Research in Onco-Hematology, Faculty of Medicine, University of Geneva, Swiss Cancer Center Leman, Geneva, Switzerland. 949979 author De Vito Claudio Division of Clinical Pathology, Department of Diagnostics, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 795706 author Labidi-Galy Sana Intidhar Department of Medicine and Center of Translational Research in Onco-Hematology, Faculty of Medicine, University of Geneva, Swiss Cancer Center Leman, Geneva, Switzerland.,Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 817058 Département de médecine (DEMED) author Kandalaft Lana E 0000-0002-1575-6674 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.,Center of Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Dangaj Laniti Denarda Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. author Bassani-Sternberg Michal 0000-0002-1934-954X Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.,Center of Experimental Therapeutics, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Oliveira Giacomo 0000-0001-7435-5603 Dana-Farber Cancer Institute, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA.,Broad Institute of MIT and Harvard, Cambridge, MA, USA. author Wu Catherine J Dana-Farber Cancer Institute, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA.,Broad Institute of MIT and Harvard, Cambridge, MA, USA. author Coukos George 0000-0001-8813-7367 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.,Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. author Zoete Vincent 0000-0002-2336-6537 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland.,Molecular Modelling Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. author Harari Alexandre Max-Albert 0000-0002-1055-2090 Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland. alexandre.harari@chuv.ch.,Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. alexandre.harari@chuv.ch. 87597 10.1038/s41587-024-02232-0 38714897 1087-0156 https://www.nature.com/articles/s41587-024-02232-0 A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts. Dewey 616.07 Dewey 616 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 1388 Cancers de la femme 1040 Nature biotechnology 8799ac5e-58af-47d4-8983-d38a31d00422 Article (Published version) Public Article_scientifique_from_crossref.pdf 7403738 application/pdf CC BY-4.0 78c99eea838ae38130dd05952d4764bd714b51a8780216df6ec6f8f730d25307 6aa7819b-cc84-45ec-b261-bebe86eccf06 Erratum Public s41587-024-02318-9.pdf 525970 application/pdf CC BY-4.0 9959870fdf9f2b145f6e641e165a384b34ed5fbe2d37e49bdb5bb01d0b3678bb In the version of the article initially published, there were errors in Extended Data Fig. 5e. One patient was erroneously omitted due to an inaccurate y-axis scale, and in the key “n = 17” has been corrected to “n = 12”. 10.1038/s41587-024-02318-9 38918618 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine

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Identification of clinically relevant t cell receptors for personalized t cell therapy using combinatorial algorithms	Nature biotechnology			2024	169	74

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Barras, David