Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model
Abstract
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.
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α-PD-1/PD-L1 enhanced CAR-T cell therapy by rescuing CAR-T cell exhaustion.
“α-PD-1/PD-L1 enhanced CAR-T cell therapy by rescuing CAR-T cell exhaustion [341–343].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [342]
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- Authors
- Song, Y., Liu, Q., Zuo, T., Wei, G., & Jiao, S.
- Affiliations
- Chinese PLA General Hospital (CN)
- Corresponding author
- Jiao, Shunchang
- Venue
- Cellular Immunology
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 352
- Pages
- 104112
- ISSN
- 0008-8749 (ISSN-L)
- OpenAlex
- W3015923357
- Cited by
- 52
- References
- 26
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 13 · 2023: 6 · 2022: 12 · 2021: 6 · 2020: 3
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- glioblastoma, CAR T-cell therapy, anti-PD-1 therapy, T cell exhaustion, tumor microenvironment, tumor-infiltrating lymphocytes, combination immunotherapy, solid tumor immunotherapy
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Disease Models, Animal, Female, Glioblastoma, Humans, Mice, Nude, T-Lymphocytes, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Tumor Microenvironment, Programmed Cell Death 1 Receptor, ErbB Receptors
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