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Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies

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Summary

T-cell malignancies often result in poor prognosis and outcome for patients. Immunotherapy has recently emerged as a revolutionary treatment against cancer, and the success seen in CD19 CAR clinical trials may extend to T cell diseases. However, a shared antigen pool coupled with the impact of T-cell depletion incurred by targeting T cell disease remain concepts to be clinically explored with caution. Here we report on the ability of T cells transduced with a CD5CAR to specifically and potently lyse malignant T-cell lines and primary tumors in vitro in addition to significantly improving in vivo control and survival of xenograft models of T-ALL. To extensively explore and investigate the biological properties of a CD5 CAR, we evaluated multiple CD5 CAR constructs and constructed 3 murine models to characterize the properties of CD5 down-regulation, the efficacy and specificity produced by different CD5 CAR construct designs, and the impact of incorporating a CD52 safety switch using CAMPATH to modulate the persistency and function of CAR cells. These data support the potential use of CD5CAR T cells in the treatment of T cell malignancies or refractory disease in clinical settings.

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Acknowledgements

We thank Todd Rueb and Rebecca Connor at the Stony Brook University Flow Cytometry Core Facility for technical advice and assistance. We also thank Laurie Levine and Joan Pashinsky in Stony Brook University animal facility for assistance with animal care.

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Authors and Affiliations

  1. iCell Gene Therapeutics LLC Research & Development Division, Long Island High Technology Incubator, 25 Health Sciences Drive, Stony Brook, NY, 11790, USA

    Masayuki Wada, Charlotte Olivia Tse, Sha Sha, Yuanzhen Cao, Kevin H. Chen, Kevin G. Pinz, Xun Jiang & Yupo Ma

  2. Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China

    Hongyu Zhang, Jia Feng, Wenli Zhang & Qi Chen

  3. Department of Hematology, Chengdu Military General Hospital, Chengdu, Sichuan, People’s Republic of China

    Liu Fang

  4. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China

    Xi Chen, Xing-Xing Fan & Yupo Ma

  5. Department of Pathology, Stony Brook Medicine, Stony Brook, NY, 11794, USA

    Yupo Ma

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  1. Masayuki Wada
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  2. Hongyu Zhang
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  3. Liu Fang
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  15. Yupo Ma
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Correspondence to Hongyu Zhang or Yupo Ma.

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Y.M. is a cofounder of iCell Gene Therapeutics, LLC.

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Figure S1

Relative titer of CD5CAR-3G lentivirus (JPG 1259 kb)

Figure S2

CD5CAR and anchored CD5CAR constructs induce downregulation of self-CD5 surface expression without modulating CD5 decrease on nearby cells in co-cultures (JPG 3853 kb)

Figure S3

CD5CAR-3G T cells suppress CCRF-CEM expansion in vivo (JPG 999 kb)

Figure S4

Persistence of CCRF-CEM cells in mouse peripheral blood. (A) (JPG 1218 kb)

Figure S5

CD52 co-expressed CD5CAR-28 and CD5CAR-3G T cells lyse CD5 positive T-ALL cell lines and normal T cells as well as CD5CAR-3G T cells. (JPG 4550 kb)

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Wada, M., Zhang, H., Fang, L. et al. Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies. Stem Cell Rev and Rep 16, 369–384 (2020). https://doi.org/10.1007/s12015-019-09937-9

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