Contributors: LabEX IGO Immunothérapie Grand Ouest; Centre de Recherche en Cancérologie Nantes-Angers (CRCNA); Centre Hospitalier Universitaire d'Angers (CHU Angers); PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes); Plateforme MicroPicel; Université de Nantes (UN); This work has been supported by INSERM, CNRS, Université de Nantes, Association pour la Recherche contre le Cancer (#R10139NN), Institut National du Cancer (#V9V2THER, INCa #PLBio2013-201, #PLBio2014-155), Agence Nationale de la Recherche (ANR, #GDSTRESS),LigueNationalecontreleCancer(AOInterRegional2012).; ANR-12-BSV3-0024,GDSTRESS,Détection du stress cellulaire par les lymphocytes T gamma/delta humains(2012); ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011); ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010); Nantes Université (Nantes Univ)
نبذة مختصرة : Glioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor. Aggressive treatment still fails to eliminate deep brain infiltrative and highly resistant tumor cells. Human Vγ9Vδ2 T cells, the major peripheral blood γδ T cell subset, react against a wide array of tumor cells and represent attractive immune effector T cells for the design of antitumor therapies. This study aims at providing a preclinical rationale for immunotherapies in GBM based on stereotaxic administration of allogeneic human Vγ9Vδ2 T cells. The feasibility and the antitumor efficacy of stereotaxic Vγ9Vδ2 T cell injections have been investigated in orthotopic GBM mice model using selected heterogeneous and invasive primary human GBM cells. Allogeneic human Vγ9Vδ2 T cells survive and patrol for several days within the brain parenchyma following adoptive transfer and can successfully eliminate infiltrative GBM primary cells. These striking observations pave the way for optimized stereotaxic antitumor immunotherapies targeting human allogeneic Vγ9Vδ2 T cells in GBM patients.
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