Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia
Por:
Martinez, DS, Tirado, N, Mensurado, S, Martinez-Moreno, A, Romecin, P, Aguera, FG, Correia, DV, Silva-Santos, B and Menendez, P
Publicada:
1 sep 2022
Resumen:
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 V delta 1(+)gamma delta 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-3 alpha 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.
Filiaciones:
:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
Mensurado, S:
Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, Lisbon, Portugal
Martinez-Moreno, A:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
Correia, DV:
Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, Lisbon, Portugal
Silva-Santos, B:
Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, Lisbon, Portugal
:
Univ Barcelona, Sch Med, Josep Carreras Leukaemia Res Inst, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III ISCII, Red Espanola Teraplas Avanzadas TERAV, Madrid, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Oncol CIBERONC, Barcelona, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain
gold, Green Published, Green Submitted
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