Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia
| العنوان: | Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia |
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| المؤلفون: | Depei Wu, Lei Yu, Yanming Zhang, Guoqiang Lin |
| المصدر: | Molecular Medicine Reports |
| بيانات النشر: | Spandidos Publications, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, THP-1 Cells, medicine.medical_treatment, Programmed Cell Death 1 Receptor, acute myeloid leukemia, Biochemistry, C-type lectin-like molecule-1, 03 medical and health sciences, 0302 clinical medicine, Antigen, immune system diseases, hemic and lymphatic diseases, Genetics, medicine, Humans, Cytotoxic T cell, Gene Silencing, Acute monocytic leukemia, CD371, neoplasms, Molecular Biology, Receptors, Chimeric Antigen, chimeric antigen receptor, business.industry, CD28, Myeloid leukemia, Articles, Immunotherapy, medicine.disease, Adoptive Transfer, Leukemia, Myeloid, Acute, 030104 developmental biology, medicine.anatomical_structure, Oncology, programmed cell death 1, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Bone marrow, K562 Cells, business, CD8 |
| الوصف: | 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. |
| تدمد: | 1791-3004 1791-2997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8664b5b3bf1227696da793080e04864d https://doi.org/10.3892/mmr.2021.11847 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8664b5b3bf1227696da793080e04864d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17913004 17912997 |
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