Fiche publication
Date publication
février 2020
Journal
Leukemia
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
,
Dr BINDA Delphine
,
Pr DECONINCK Eric
,
Dr FERRAND Christophe
,
Pr GARNACHE-OTTOU Francine
,
Dr GODET Yann
,
Dr DESCHAMPS Marina
,
Dr DAGUINDAU Etienne
,
Dr ANGELOT-DELETTRE Fanny
,
Dr MOLIMARD Chloé
Tous les auteurs :
Bôle-Richard E, Fredon M, Biichlé S, Anna F, Certoux JM, Renosi F, Tsé F, Molimard C, Valmary-Degano S, Jenvrin A, Warda W, Pallandre JR, Bonnefoy F, Poussard M, Deschamps M, Petrella T, Roumier C, Macintyre E, Féger F, Brissot E, Mohty M, HoWangYin KY, Langlade-Demoyen P, Loustau M, Caumartin J, Godet Y, Binda D, Pagadoy M, Deconinck E, Daguindau E, Saas P, Ferrand C, Angelot-Delettre F, Adotévi O, Garnache-Ottou F
Lien Pubmed
Résumé
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is associated with a remarkably poor prognosis and with no treatment consensus. The identification of relevant therapeutic targets is challenging. Here, we investigated the immune functions, antileukemia efficacy and safety of CD28/4-1BB CAR T cells targeting CD123 the interleukin (IL)-3 receptor alpha chain which is overexpressed on BPDCN. We demonstrated that both retroviral and lentiviral engineering CD28/4-1BB CD123 CAR T cells exhibit effector functions against BPDCN cells through CD123 antigen recognition and that they efficiently kill BPDCN cell lines and BPDCN-derived PDX cells. In vivo, CD28/4-1BB CD123 CAR T-cell therapy displayed strong efficacy by promoting a decrease of BPDCN blast burden. Furthermore we showed that T cells from BPDCN patient transduced with CD28/4-1BB CD123 CAR successfully eliminate autologous BPDCN blasts in vitro. Finally, we demonstrated in humanized mouse models that these effector CAR T cells exert low or no cytotoxicity against various subsets of normal cells with low CD123 expression, indicating a potentially low on-target/off-tumor toxicity effect. Collectively, our data support the further evaluation for clinical assessment of CD28/4-1BB CD123 CAR T cells in BPDCN neoplasm.
Référence
Leukemia. 2020 Feb 28;:
