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

Authors:He, Xin; Feng, Zijie; Ma, Jian; Ling, Sunbin; Cao, Yan; Gurung, Buddha; Wu, Yuan; Katona, Bryson W; O'Dwyer, Kienan P; Siegel, Don L; June, Carl H; Hua, Xianxin
Source:Blood, 2020, 135(10): 713-723.
DOI:10.1182/blood.2019002779

Summary

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.

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