ArticleCancer immunology, immunotherapy : CII2024
Incorporating IL7 receptor alpha signaling in the endodomain of B7H3-targeting chimeric antigen receptor T cells mediates antitumor activity in glioblastoma.
Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.World journal of clinical oncology · 2026Review
- Integrative Multi-Omics Analysis Reveals Molecular Signatures of Recurrence in Paired Primary and Recurrent High-Grade Serous Ovarian Cancer.International journal of molecular sciences · 2026Article
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Loss of Fibronectin Fiber Tension in Glioblastoma is Associated with Microvascular Proliferations and Immune Cell Infiltration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.Nature reviews. Gastroenterology & hepatology · 2025Review
- Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.Current issues in molecular biology · 2025Review
- Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study.Journal for immunotherapy of cancer · 2025Article
- Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- IL-7: a potential next-generation adjuvant for immune cell therapies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
CAR-T-cell therapy has shown promise in treating hematological malignancies but faces challenges in treating solid tumors due to impaired T-cell function in the tumor microenvironment. To provide optimal T-cell activation, we developed a B7 homolog 3 protein (B7H3)-targeting CAR construct consisting of three activation signals: CD3ζ (signal 1), 41BB (signal 2), and the interleukin 7 receptor alpha (IL7Rα) cytoplasmic domain (signal 3). We generated B7H3 CAR-T cells with different lengths of the IL7Rα cytoplasmic domain, including the full length (IL7R-L), intermediate length (IL7R-M), and short length (IL7R-S) domains, and evaluated their functionality in vitro and in vivo. All the B7H3-IL7Rα CAR-T cells exhibited a less differentiated phenotype and effectively eliminated B7H3-positive glioblastoma in vitro. Superiority was found in B7H3 CAR-T cells contained the short length of the IL7Rα cytoplasmic domain. Integration of the IL7R-S cytoplasmic domain maintained pSTAT5 activation and increased T-cell proliferation while reducing activation-induced cell death. Moreover, RNA-sequencing analysis of B7H3-IL7R-S CAR-T cells after coculture with a glioblastoma cell line revealed downregulation of proapoptotic genes and upregulation of genes associated with T-cell proliferation compared with those in 2nd generation B7H3 CAR-T cells. In animal models, compared with conventional CAR-T cells, B7H3-IL7R-S CAR-T cells suppressed tumor growth and prolonged overall survival. Our study demonstrated the therapeutic potential of IL7Rα-incorporating CAR-T cells for glioblastoma treatment, suggesting a promising strategy for augmenting the effectiveness of CAR-T cell therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.