Journal
BLOOD
Volume 135, Issue 10, Pages 713-723Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019002779
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Funding
- National Institutes of Health, National Cancer Institute [R01-CA-178856]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK097555]
- American Association for Cancer Research-Neuroendocrine Tumor Research Foundation
- Harrington Discovery Institute Takeda Rare Disease Scholar award
- Clinical and Translational Research Award-Institute for Translational Medicine and Therapeutics pilot grant at the University of Pennsylvania
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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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