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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.

SUBMITTER: He X

PROVIDER: S-EPMC7059518 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

He Xin X Feng Zijie Z Ma Jian J Ling Sunbin S Cao Yan Y Gurung Buddha B Wu Yuan Y Katona Bryson W BW O'Dwyer Kienan P KP Siegel Don L DL June Carl H CH Hua Xianxin X

Blood 20200301 10

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, ...[more]

PMID: 31951650

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