HARARI Lab
Our focus
Our objective is to unveil the dynamic of T-cell specificities and antigen recognition in patients receiving cellular therapies and to develop new knowledge and methods leading to early clinical translation in the domain of T-cell therapy.
Our projects
- We have designed novel culture methods to generate tumor-infiltrating lymphocyte (TILs) populations that are highly enriched in neoepitope-specific CD8 T cells.
- We have developed sensitive and high-throughput methodologies to interrogate T cells and analyze repertoires of T cell receptors (TCRs) and have developed unique functional assays to profile tumor antigen-specific T cells.
- We have established a multidisciplinary consortium (FNS Synergia), including bio-engineering and bioinformatics, to interrogate antitumoral immunity and to develop next-generation cellular immunity.
- We have established mass cytometry analyses on tissue and cell suspension to interrogate human samples of patients undergoing T cell therapy.
- We also use single cell sequencing (RNA and TCRs) to profile patients adoptively transferred with autologous TILs to understand the dynamic of individual clonotypes in vitro (during TIL expansion) and in vivo (after infusion to patients).
KEY PUBLICATIONS
- J. Schmidt, J. Chiffelle, M. A. S. Perez, M. Magnin, S. Bobisse, M. Arnaud, R. Genolet, … V. Zoete, G. Coukos, A. Harari. Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors. Nature Communications (2023).
- R. Genolet, S. Bobisse, J. Chiffelle, M. Arnaud, … G. Coukos, A. Harari. Novel TCR sequencing and cloning methods for sensitive and quantitative interrogation of repertoires and rapid isolation of tumor-reactive TCRs. Cell Report Methods (2023).
- M. Arnaud, J. Chiffelle... S. Bobisse, G. Coukos, A. Harari. Sensitive identification of neoantigens and cognate TCRs in human solid tumors. Nature Biotechnology (2022).
- M. Bassani-Sternberg & A. Harari. Immune pressure sculps tumor cells and trims high-quality mutations. Cancer Cell (2022).
- A. Harari, M. Graciotti, M. Bassani & L.E. Kandalaft. Mobilizing and potentiating antitumor immunity using dendritic cell vaccination in a novel priming and boosting approach. Nature Drug Discovery Review (2020).
- J.R. Devlin, J.A. Alonso, G.L.J. Keller, S. Bobisse, C.W. Vander Kooi, G. Coukos, D. Gfeller, A. Harari & B.M. Baker. Structural dissimilarity to self drives neoepitope escape from immune tolerance. Nature Chemical Biology (2020).
- S. Bobisse,…G. Coukos, A. Harari. Sensitive and Frequent Identification of High Avidity Neo-epitope Specific CD8+ T-cells in Immunotherapy-naïve Ovarian Cancer. Nature Communications (2018).
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