Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia
- Guoqiang Lin
- Yanming Zhang
- Lei Yu
- Depei Wu
Affiliations: National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Hematology, Huai'an Hospital Affiliated to Xuzhou Medical College, Huai'an Second People's Hospital, Huai'an, Jiangsu 223002, P.R. China, Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200065, P.R. China
- Published online on: January 18, 2021 https://doi.org/10.3892/mmr.2021.11847
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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.