P10

Development of 𝛾𝛿 T cells immunotherapy against glioblastoma

G Marseres(1) C Gentil(1) D Bomont(5) V Bigot(2) M Courant(2) V Prouzet-Mauleon(3) V Pitard(1,3) A Zouine(3) S Mensurado(4) C Larrieu(5) B Turcq(3) B Silva-Santos(4) J Engelhardt(2) L Couzi(1,2) T Daubon(5) J Dechanet-Merville(1)

1:Univeristé de Bordeaux, ImmunoConcept UMR5164; 2:Bordeaux University Hospital; 3:Université de Bordeaux INSERM UMS3427 TBMCore; 4:Instituto de medicina molecular, Universidade de Lisboa; 5:Université de Bordeaux CNRS IBGC UMR5095

γδ T cells are unconventional T cells harboring features of innate and adaptive response. Indeed, they express both TCR receptors (although interacting with their target in a mostly MHC independent manner) and NK receptors, conferring them cytotoxic characteristics. They are besides, specifically enriched in tissues and their number in tumors associates with better survival in different solid cancers. As such, clinical scale in-vitro expanded γδ T cells are currently in clinical trials. Their characteristics make them of great interest to develop as therapeutic agent particularly in tumors with low mutational burden or low HLA-I expression, such as Glioblastomas (GBM). So far, immunotherapies evaluated in clinical trials have failed to provide significant clinical benefit for GBM patients, notably due to the high genetic heterogeneity and immunosuppressive environment of the tumor.

Here, we aimed at developing a new cell therapy strategy in GBM, using in-vitro expanded γδ T cells (DOT cells).

Characterization of immune cells isolated from GBM patient samples highlighted γδ T cells recruitment within tumors. In parallel, using commercially available GBM cell lines and patient-derived glioblastoma stem cells, we showed that amplified γδ T cells, used in combination with interleukin-15, could efficiently recognize and kill GBM cells and spheroids in-vitro, relying on the granule exocytosis pathway. Finally, patient-derived xenograft mouse models of GBM and γδ T cells-based therapy are showing a delay in the tumor growth in preliminary results. Altogether, our results are providing encouraging results to develop allogeneic use of γδ T cell therapies in GBM patients.