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
Bloodjournal_title
Bloodauthors
He X,Feng Z,Ma J,Ling S,Cao Y,Gurung B,Wu Y,Katona BW,O'Dwyer KP,Siegel DL,June CH,Hua Xdoi
10.1182/blood.2019002779subject
Has Abstractpub_date
2020-03-05 00:00:00pages
713-723issue
10eissn
0006-4971issn
1528-0020pii
431045journal_volume
135pub_type
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