ArticleCancers2021
Cytolytic Activity of CAR T Cells and Maintenance of Their CD4+ Subset Is Critical for Optimal Antitumor Activity in Preclinical Solid Tumor Models.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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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.
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Who cites it
17 citing papers in PubMed.
- Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Ten years of translational innovation in HER2-targeted immune cell therapy - A comprehensive review of the work of the University of Debrecen Cell and Molecular Therapy Research Group.Magyar onkologia · 2026Review
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- CAR-T manufacturing reduces heterogeneity between CIDP and multiple myeloma patient-derived T cells.Theranostics · 2026Article
- Article
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Inhibition of KCancers · 2024Article
- Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.World journal of methodology · 2024Review
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Choosing T-cell sources determines CAR-T cell activity in neuroblastoma.Frontiers in immunology · 2024Article
- Universal CAR T cells targeted to HER2 with a biotin-trastuzumab soluble linker penetrate spheroids and large tumor xenografts that are inherently resistant to trastuzumab mediated ADCC.Frontiers in immunology · 2024Article
- CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.Nature reviews. Clinical oncology · 2024Review
- Characterization of chimeric antigen receptor modified T cells expressing scFv-IL-13Rα2 after radiolabeling withJournal of translational medicine · 2023Article
- Article
- Lineage tracing of T cell differentiation from T-iPSC by 2D feeder-free culture and 3D organoid culture.Frontiers in immunology · 2023Article
- The generation and application of antigen-specific T cell therapies for cancer and viral-associated disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- CAR-T Cell Performance: How to Improve Their Persistence?Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Correlative studies of clinical studies for hematological malignancies have implicated that less differentiated, CD8+-dominant CAR T cell products have greater antitumor activity. Here, we have investigated whether the differentiation status of CAR T cell products affects their antitumor activity in preclinical models of solid tumors. We explored if different activation/expansion protocols, as well as different co-stimulatory domains in the CAR construct, influence the short- and long-term efficacy of CAR T cells against HER2-positive tumors. We generated T cell products that range from the most differentiated (CD28.z; OKT3-antiCD28/RPMI expansion) to the least differentiated (41BB.z; OKT3-RetroNectin/LymphoONE expansion), as judged by cell surface expression of the differentiation markers CCR7 and CD45RA. While the effect of differentiation status was variable with regard to antigen-specific cytokine production, the most differentiated CD28.z CAR T cell products, which were enriched in effector memory T cells, had the greatest target-specific cytolytic activity in vitro. These products also had a greater proliferative capacity and maintained CD4+ T cells upon repeated stimulation in vitro. In vivo, differentiated CD28.z CAR T cells also had the greatest antitumor activity, resulting in complete response. Our results highlight that it is critical to optimize CAR T cell production and that optimal product characteristics might depend on the targeted antigen and/or cancer.
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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.