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IL‐33‐expanded human Vγ9Vδ2 T cells have anti‐lymphoma effect in a mouse tumor model
Authors:Caroline Duault  Delphine Betous  Christine Bezombes  Stéphane Roga  Corinne Cayrol  Jean‐Philippe Girard  Jean‐Jacques Fournié  Mary Poupot
Affiliation:1. INSERM UMR1037‐Cancer Research Center of Toulouse, Toulouse, France;2. ERL 5294 CNRS, Toulouse, France;3. Université Toulouse III Paul‐Sabatier, Toulouse, France;4. Laboratoire d'excellence Toucan;5. Stanford University School of Medicine, Stanford, CA, USA;6. CNRS UMR 5089, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France
Abstract:From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell‐based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL‐2, which is essential for the combination therapy with Phosphoantigen (PAg). Recently, we showed that IL‐33, a γ chain receptor‐independent cytokine, was able to induce the in vitro proliferation of PAg‐activated Vγ9 T cells, which were fully functional expressing IFN‐γ and TNF‐α and showing in vitro anti‐tumor cytotoxicity. We proposed IL‐33 as an alternative to IL‐2 for Vγ9 T cell‐based cancer immunotherapies, and have therefore evaluated the efficacy of this cytokine in preclinical investigations. This study shows that human Vγ9 T cells are able to proliferate in a mouse model with the combination of PAg and rhIL‐33, and that IL‐33‐expanded Vγ9 T cells can prevent tumor growth in a mouse lymphoma model.
Keywords:Cancer  Immunotherapy  IL‐33  Lymphoma  Phosphoantigens    9Vδ  2
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