ArticlePloS one2015
Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- A new strategy for CAR-T therapy in solid tumors: IL-15-autocrine signaling augments tumor stroma depletion and promotes a TCell death & disease · 2025Article
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Exploring CAR-PBMCs: A Novel Strategy Against EGFR-Positive Tumor Cells.Biomedicines · 2025Article
- Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.Cell death & disease · 2024Review
- Review
- The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation.Cancer cell international · 2023Article
- Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells.Immunity · 2023Article
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Review
- DIALing-up the preclinical characterization of gene-modified adoptive cellular immunotherapies.Frontiers in immunology · 2023Review
- CAR-T cell combination therapy: the next revolution in cancer treatment.Cancer cell international · 2022Review
- The next wave of cellular immunotherapies in pancreatic cancer.Molecular therapy oncolytics · 2022Review
- Engineering CAR T cells for enhanced efficacy and safety.APL bioengineering · 2022Review
- Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer.Immunotherapy advances · 2022Review
- Bispecific CAR T Cells against EpCAM and Inducible ICAM-1 Overcome Antigen Heterogeneity and Generate Superior Antitumor Responses.Cancer immunology research · 2021Article
- CAR T-Cell Therapy in Hematological Malignancies.International journal of molecular sciences · 2021Review
- Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma.Molecular therapy oncolytics · 2021Article
- How Can We Engineer CAR T Cells to Overcome Resistance?Biologics : targets & therapy · 2021Review
- Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy.Biologics : targets & therapy · 2021Review
- CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Adoptive T cell therapy represents a promising treatment for cancer. Human T cells engineered to express a chimeric antigen receptor (CAR) recognize and kill tumor cells in a MHC-unrestricted manner and persist in vivo when the CAR includes a CD28 costimulatory domain. However, the intensity of the CAR-mediated CD28 activation signal and its regulation by the CTLA-4 checkpoint are unknown. We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z) displayed the same proliferation and anti-tumor abilities than T cells expressing a CD3 zeta-based CAR (19z1) costimulated through the CD80/CD28, ligand/receptor pathway. Repeated in vitro antigen-specific stimulations indicated that 19-28z+ T cells secreted higher levels of Th1 cytokines and showed enhanced proliferation compared to those of 19z1+ or 19z1-CD80+ T cells. In an aggressive pre-B cell leukemia model, mice treated with 19-28z+ T cells had 10-fold reduced tumor progression compared to those treated with 19z1+ or 19z1-CD80+ T cells. shRNA-mediated CTLA-4 down-regulation in 19z1-CD80+ T cells significantly increased their in vivo expansion and anti-tumor properties, but had no effect in 19-28z+ T cells. Our results establish that CTLA-4 down-regulation may benefit human adoptive T cell therapy and demonstrate that CAR design can elude negative checkpoints to better sustain T cell function.
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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.