ArticleCancers2021
CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 38 citations in OpenAlex.
- Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies.Cancer cell · 2026Article
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- Chimeric antigen receptor T cell targeting CD44E variant in HCC holds therapeutic potential.Molecular therapy. Oncology · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Ionizing radiation enhances CAR T-cell infiltration and efficacy in solid tumors.Frontiers in immunology · 2026Article
- CAR T-cells for the treatment of CNS malignancies.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.Cancer immunology research · 2025Article
- [CAR T cells in solid tumors: resistance mechanisms].Innere Medizin (Heidelberg, Germany) · 2025Review
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.Nature reviews. Gastroenterology & hepatology · 2025Review
- IFN-γ-resistant CD28 CAR T cells demonstrate increased survival, efficacy, and durability in multiple murine tumor models.Science translational medicine · 2025Article
- NKG2D/CD28 chimeric receptor boosts cytotoxicity and durability of CAR-T cells for solid and hematological tumors.Experimental hematology & oncology · 2025Article
- Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.Cancer cell international · 2024Review
- Tuning spacer length improves the functionality of the nanobody-based VEGFR2 CAR T cell.BMC biotechnology · 2024Article
- CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.Nature reviews. Clinical oncology · 2024Review
- Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.Nature immunology · 2024Article
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Spacer or co-stimulatory components in chimeric antigen receptor (CAR) design influence CAR T cell effector function. Few preclinical mouse models optimally support CAR candidate pre-selection for clinical development. Here we use a model in which murine CAR T cells can be exploited with human tumor xenografts. This mouse-in-mouse approach avoids limitations caused by species-specific factors crucial for CAR T cell survival, trafficking and function. We compared trafficking, expansion and tumor control for T cells expressing different CAR construct designs targeting two antigens (L1CAM or HER2), structurally identical except for spacer (long or short) or co-stimulatory (4-1BB or CD28) domains to be evaluated. Using monoclonal, murine-derived L1CAM-specific CAR T cells in Rag-/- mice harboring established xenografted tumors from a human neuroblastoma cell line revealed a clear superiority in CAR T cell trafficking using CD28 co-stimulation. L1CAM-targeting short spacer-CD28/ζ CAR T cells expanded the most at the tumor site and induced initial tumor regression. Treating patient-derived neuroblastoma xenografts with human L1CAM-targeting CAR T cells confirmed the superiority of CD28 co-stimulus. CD28 superiority was also demonstrated with HER2-specific CAR T cells (targeting ovarian carcinoma xenografts). Our findings encourage incorporating CD28 signaling into CAR design for adoptive T cell treatment of solid tumors.
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Identifiers
What OpenQuestion holds
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.