Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model
| Autor: | Shunchang Jiao, Tong Zuo, Yujie Song, Guoyan Wei, Qingtian Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
T cell T-Lymphocytes Immunology Cell Programmed Cell Death 1 Receptor Mice Nude Biology Immunotherapy Adoptive Cell therapy 03 medical and health sciences Mice 0302 clinical medicine Lymphocytes Tumor-Infiltrating Cell Line Tumor medicine Tumor Microenvironment Animals Humans Tumor microenvironment Receptors Chimeric Antigen Tumor-infiltrating lymphocytes Xenograft Model Antitumor Assays In vitro Chimeric antigen receptor Blockade ErbB Receptors Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cancer research Female Glioblastoma human activities 030215 immunology |
| Zdroj: | Cellular immunology. 352 |
| ISSN: | 1090-2163 |
| Popis: | Glioblastoma is one of the deadliest cancers. Chimeric antigen receptor (CAR)-T cell therapy against solid tumors has been far from satisfactory largely due to the immunosuppressive tumor microenvironment, such as PD-1 mediated T cell exhaustion. In the present study, we investigated the combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model. The results demonstrated that CAR-T cells with PD-1 blockade exhibit higher killing efficiency in vitro. Additionally, CAR-T cells with PD-1 blockade showed more effective and persistent therapeutic effects on glioblastoma and led to significantly increased number of tumor infiltrating lymphocytes (TILs) in the mouse model. In conclusion, PD-1 checkpoint blockade significantly enhanced the antitumor activity of anti-human EGFRvIII CAR-T cells by overcoming TILs exhaustion. The outcomes of the present study provide a novel strategy for improving the potency of CAR-T cell therapies in solid tumors. |
| Databáze: | OpenAIRE |
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