ArticleScience advances2024
TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed.
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.Journal of ovarian research · 2026Review
- CD147 regulates CD8iScience · 2026Article
- Targeting fibroblast activation protein in solid tumors via LNP-mediated CAR-mRNA delivery promotes durable regression in murine models.Scientific reports · 2025Article
- The B7-H3 (CD276) pathway: emerging biology and clinical therapeutics.Trends in pharmacological sciences · 2025Review
- Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.Current issues in molecular biology · 2025Review
- Diverse potential of chimeric antigen receptor-engineered cell therapy: Beyond cancer.Clinical and translational medicine · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Tumor Immunotherapy Targeting B7-H3: From Mechanisms to Clinical Applications.ImmunoTargets and therapy · 2025Review
- The broad spectrum of cancer and immunotherapy: achievements and limitations.Frontiers in immunology · 2025Review
- Advances in CAR-T therapy for central nervous system tumors.Biomarker research · 2024Review
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cell therapy shows impressive efficacy treating hematologic malignancies but requires further optimization in solid tumors. Here, we developed a TMIGD2 optimized potent/persistent (TOP) CAR that incorporated the costimulatory domain of TMIGD2, a T and NK cell costimulator, and monoclonal antibodies targeting the IgV domain of B7-H3, an immune checkpoint expressed on solid tumors and tumor vasculature. Comparing second- and third-generation B7-H3 CARs containing TMIGD2, CD28, and/or 4-1BB costimulatory domains revealed superior antitumor responses in B7-H3.TMIGD2 and B7-H3.CD28.4-1BB CAR-T cells in vitro. Comparing these two constructs using in vivo orthotopic human cancer models demonstrated that B7-H3.TMIGD2 CAR-T cells had equivalent or superior antitumor activity, survival, expansion, and persistence. Mechanistically, B7-H3.TMIGD2 CAR-T cells maintained mitochondrial metabolism; produced less cytokines; and established fewer exhausted cells, more central memory cells, and a larger CD8/CD4 T cell ratio. These studies demonstrate that the TOP CAR with TMIGD2 costimulation offered distinct benefits from CD28.41BB costimulation and is effective against solid tumors.
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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.