The DOI matches its Crossref record; 73 of the 75 references it cites were found in a registry or an index.
Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity
Open accessAbstract
Chimeric antigen receptor–modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4 + and CD8 + subsets. Here, we investigated the differential antitumor effect of CD4 + and CD8 + CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2 + GBM cells, the CD8 + CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4 + CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4 + CAR T cells failed to ameliorate the effector dysfunction of CD8 + CAR T cells, while surprisingly, CD4 + CAR T cell effector potency was impaired when coapplied with CD8 + T cells. In orthotopic GBM models, CD4 + outperformed CD8 + CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4 + subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4 + CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.
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“For example, release of Th1 and Th2 cytokines by activated CD4+ T helper (Th) cells supports tumor cell killing by cytotoxic T cells, macrophages and granulocytes212.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [212]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Wnt signalling in stem cells and cancer
Reya, T., & Clevers, H. (2005) · Nature · doi:10.1038/nature03319 · Cited by 3,666
Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Turtle, C. J., Hanafi, L.-A., Berger, C., Gooley, T. A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T. M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85309 · Cited by 2,112
Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.001 · Cited by 2,096
Brentjens, R. J., Davila, M. L., Riviere, I., Park, J., Wang, X., Cowell, L. G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005930 · Cited by 2,063
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Self-citationThe landscape of the mesenchymal signature in brain tumours
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Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy
Basu, A. B., Ramamoorthi, G., Albert, G. K., Gallen, C., Beyer, A., Snyder, C., Koski, G. K., Disis, M. L., Czerniecki, B. J., & Kodumudi, K. N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.669474 · Cited by 329
Metadata
- Authors
- Wang, D., Aguilar, B., Starr, R., Alizadeh, D., Brito, A., Sarkissian, A., Ostberg, J. R., Forman, S. J., & Brown, C. E.
- Affiliations
- City Of Hope National Medical Center (US)
- CTI BioPharma (United Kingdom) (GB)
- Corresponding author
- Brown, Christine E.
- ORCID
- Venue
- JCI Insight
- Published
- 2018-05-17
- Volume
- 3
- Issue
- 10
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC6012522
- OpenAlex
- W2803369586
- Cited by
- 233
- References
- 75
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 26 · 2023: 36 · 2022: 40 · 2021: 33 · 2020: 27 · 2019: 26 · 2018: 3
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute for Regenerative Medicine (TR3-05641)
- National Cancer Institute (P30 CA33572)
- U.S. Food and Drug Administration (1R01FD005129-01)
- Gateway for Cancer Research (G-14-600)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- glioblastoma, chimeric antigen receptor T cells, CD4+ T cells, CD8+ T cells, IL-13 receptor alpha 2, CAR-T cell exhaustion, T cell persistence, T cell co-culture, antitumor immunity, solid tumor immunotherapy
- MeSH terms
- Glioblastoma, Humans, CD8-Positive T-Lymphocytes
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