Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia
Sánchez Martínez, Diego (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tirado, Nestor (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Mensurado, Sofía (Universidade de Lisboa)
Martínez Moreno, Alba (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Romecín, Paola Alejandra (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Gutiérrez-Agüera, Francisco (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Correia, Daniel V. (Universidade de Lisboa)
Silva-Santos, Bruno (Universidade de Lisboa)
Menéndez Bujan, Pablo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Data:	2022
Resum:	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 patientderived 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.
Ajuts:	"la Caixa" Foundation LCF/PR/HR19/52160011
Drets:
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Journal for immunotherapy of cancer, Vol. 10 Núm. 9 (september 2022) , p. e005400, ISSN 2051-1426

DOI: 10.1136/jitc-2022-005400
PMID: 36162920

13 p, 6.9 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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