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Blood ; 135(10): 713-723, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31951650

RESUMO

Chimeric antigen receptor (CAR) T cells have radically improved the treatment of B cell-derived malignancies by targeting CD19. The success has not yet expanded to treat acute myeloid leukemia (AML). We developed a Sequentially Tumor-Selected Antibody and Antigen Retrieval (STAR) system to rapidly isolate multiple nanobodies (Nbs) that preferentially bind AML cells and empower CAR T cells with anti-AML efficacy. STAR-isolated Nb157 specifically bound CD13, which is highly expressed in AML cells, and CD13 CAR T cells potently eliminated AML in vitro and in vivo. CAR T cells bispecific for CD13 and TIM3, which are upregulated in AML leukemia stem cells, eradicated patient-derived AML, with much reduced toxicity to human bone marrow stem cells and peripheral myeloid cells in mouse models, highlighting a promising approach for developing effective AML CAR T cell therapy.


Assuntos
Leucemia Mieloide Aguda , Receptores de Antígenos de Linfócitos T , Animais , Antígenos CD13 , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Imunoterapia Adotiva , Camundongos , Linfócitos T
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