Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

He X,Feng Z,Ma J,Ling S,Cao Y,Gurung B,Wu Y,Katona BW,O'Dwyer KP,Siegel DL,June CH,Hua X

doi

10.1182/blood.2019002779

subject

Has Abstract

pub_date

2020-03-05 00:00:00

pages

713-723

issue

10

eissn

0006-4971

issn

1528-0020

pii

431045

journal_volume

135

pub_type

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