Open Access

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

  • Authors:
    • Guoqiang Lin
    • Yanming Zhang
    • Lei Yu
    • Depei Wu
  • View Affiliations

  • Published online on: January 18, 2021     https://doi.org/10.3892/mmr.2021.11847
  • Article Number: 208
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The activation of chimeric antigen receptor (CAR)‑T cells can lead to persistently high levels of programmed cell death 1 (PD‑1) antigen and eventually causes the exhaustion of T cells. The effectiveness of CAR‑T cells targeting C‑type lectin‑like molecule‑1 (CLL‑1) combined with PD‑1 silencing therapy for acute myeloid leukemia (AML) was evaluated in the present study. CLL‑1 levels in primary AML bone marrow samples was examined using flow cytometric analysis. We designed a CLL‑1 CAR‑T, containing CLL‑1‑specific single‑chain variable fragment, CD28, OX40, CD8 hinge and TM and CD3‑ζ signaling domains. CLL‑1 CAR‑T with PD‑1 silencing was constructed. It was confirmed that CLL‑1 is expressed on the surface of AML cells. CLL‑1 CAR‑T showed specific lysing activity against CLL‑1+ AML cells. PD‑1 silencing enhanced the killing ability of CLL‑1 CAR‑T. Furthermore, it was found that CAR‑T derived from healthy donor T cells was more effective in killing THP‑1 cells (a human acute monocytic leukemia cell line) than those from patient‑derived T cells. These results indicated that CLL‑1 CAR‑T and PD‑1 knockdown CLL‑1 CAR‑T could be used as a potential immunotherapy to treat relapsed or refractory AML.
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March-2021
Volume 23 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Lin G, Zhang Y, Yu L and Wu D: Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia. Mol Med Rep 23: 208, 2021.
APA
Lin, G., Zhang, Y., Yu, L., & Wu, D. (2021). Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia. Molecular Medicine Reports, 23, 208. https://doi.org/10.3892/mmr.2021.11847
MLA
Lin, G., Zhang, Y., Yu, L., Wu, D."Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia". Molecular Medicine Reports 23.3 (2021): 208.
Chicago
Lin, G., Zhang, Y., Yu, L., Wu, D."Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia". Molecular Medicine Reports 23, no. 3 (2021): 208. https://doi.org/10.3892/mmr.2021.11847