Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia
Diego Sánchez Martínez, Néstor Tirado, Sofia Mensurado, Alba Martínez-Moreno, Paola Romecín, Francisco Gutiérrez Agüera, Daniel V Correia, Bruno Silva-Santos, Pablo Menéndez
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Source: Crossref
Published: Sep 1, 2022
DOI: 10.1136/jitc-2022-005400
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Background Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell ‘fitness’ is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent Vδ1 + γδ T cells, represent a promising allogeneic platform. Methods Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. Results CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo , even on tumor rechallenge. Conclusions Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML.
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