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CAR T cells targeting CD13 controllably induce eradication of acute myeloid leukemia with a single domain antibody switch

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Fig. 1: CD13 Nb-switch redirects sCAR T cells to eradicate AML in vivo in a controllable manner.
Fig. 2: CD13 Nb-switch redirects CAR T cells to partially preserve HSCs, while still allowing eradication of PD-AML in vivo.

References

  1. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6:e441.

    Article  Google Scholar 

  2. Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–52.

    Article  Google Scholar 

  3. Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392:593–606.

    Article  Google Scholar 

  4. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.

    Article  CAS  Google Scholar 

  5. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–33.

    Article  CAS  Google Scholar 

  6. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127:3321–30.

    Article  CAS  Google Scholar 

  7. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47–62.

    Article  CAS  Google Scholar 

  8. Cummins KD, Gill S. Chimeric antigen receptor T-cell therapy for acute myeloid leukemia: how close to reality? Haematologica. 2019;104:1302–8.

    Article  CAS  Google Scholar 

  9. He X, Feng Z, Ma J, Ling S, Cao Y, Gurung B, et al. Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia. Blood. 2020;135:713–23.

    Article  Google Scholar 

  10. Raj D, Yang MH, Rodgers D, Hampton EN, Begum J, Mustafa A, et al. Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma. Gut. 2019;68:1052–64.

    Article  CAS  Google Scholar 

  11. Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, et al. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci USA. 2018;115:E10898–906.

    Article  CAS  Google Scholar 

  12. Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, et al. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci USA. 2016;113:E459–68.

    Article  CAS  Google Scholar 

  13. Ma JS, Kim JY, Kazane SA, Choi SH, Yun HY, Kim MS, et al. Versatile strategy for controlling the specificity and activity of engineered T cells. Proc Natl Acad Sci USA. 2016;113:E450–8.

    Article  CAS  Google Scholar 

  14. Ashmun RA, Look AT. Metalloprotease activity of CD13/aminopeptidase N on the surface of human myeloid cells. Blood. 1990;75:462–9.

    Article  CAS  Google Scholar 

  15. Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, Jaeger U, Lechner K, Schneider B, et al. The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Am J Clin Pathol. 2002;117:380–9.

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge that this project was supported by grants from Harrington Discovery Institute/Takeda Rare Disease Innovator Scholar award. We thank the Human Immunology Core (P30-CA016520) for the human primary T-cell processing (Supplementary Table 1), the Stem Cell and Xenograft Core at University of Pennsylvania for the patient-derived AML samples, cord blood CD34+ cells, and constructing the HIS mice.

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Authors and Affiliations

  1. Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China

    Xin He

  2. Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Xin He, Zijie Feng, Jian Ma, Xuyao Zhang, Sunbin Ling, Yan Cao, Bowen Xing, Yuan Wu, Lei Wang, Bryson W. Katona & Xianxin Hua

  3. Perelman School of Medicine, Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA

    Xin He & Carl H. June

  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June

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  1. Xin He
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  2. Zijie Feng
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  12. Xianxin Hua
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Contributions

XHe performed the experiments and generated figures. ZF made the sCAR construct. ZF, JM, XZ, YC, SL, BX, YW, LW, and BWK performed the experiments and made the discussion. CHJ analyzed and interpreted data and provided reagents. XHe and XHua analyzed data. XHua conceived and supervised the project. XHe and XHua prepared the paper. All authors commented and revised on the paper and approved the paper.

Corresponding author

Correspondence to Xianxin Hua.

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Conflict of interest

The Nb157 switch and sCAR T cells described in the paper have been included in a filed patent application by University of Pennsylvania. No other potential competing interests were disclosed.

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He, X., Feng, Z., Ma, J. et al. CAR T cells targeting CD13 controllably induce eradication of acute myeloid leukemia with a single domain antibody switch. Leukemia 35, 3309–3313 (2021). https://doi.org/10.1038/s41375-021-01208-2

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