ArticleCancer immunology research2018
Reversible Transgene Expression Reduces Fratricide and Permits 4-1BB Costimulation of CAR T Cells Directed to T-cell Malignancies.
Article in Cancer immunology research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 103 citations in OpenAlex.
- Overcoming fratricide of CD86 targeting CAR-T cells by defined logic-gate CAR strategy.Experimental hematology & oncology · 2026Article
- Generation of CCR4/CD7 Bispecific CAR-T Cells Resistant to Fratricide and Exhaustion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging Applications of CAR-T Cell Therapy in Overcoming Resistance and Expanding Targets in Hematologic Malignancies: Insights from Recent Research.Current treatment options in oncology · 2026Review
- Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor.Nature communications · 2026Article
- FAM168B identified as a novel candidate target for chimeric antigen receptor T cell-based cancer therapy.Discover oncology · 2026Review
- Rewiring T Cell Metabolism to Enhance CAR T Cell Function in Solid Tumor Microenvironments.Pharmaceutics · 2025Review
- A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity.Cell reports. Medicine · 2025Article
- Combining MCL-1 inhibition and CD37-directed chimeric antigen receptor T cells as an effective strategy to target T-cell lymphoma.Leukemia · 2025Article
- Targeting T cells with tetravalent bispecific antibodies for the treatment of graft-versus-host disease.Blood advances · 2025Article
- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors.Frontiers in immunology · 2025Review
- Fratricide-resistant CD7-CAR T cells in T-ALL.Nature medicine · 2024Article
- Antibody-Based Therapies for Peripheral T-Cell Lymphoma.Cancers · 2024Review
- CD5 deletion enhances the antitumor activity of adoptive T cell therapies.Science immunology · 2024Article
- Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.Cell reports. Medicine · 2024Article
- Advances in CAR-T-cell therapy in T-cell malignancies.Journal of hematology & oncology · 2024Review
- Chimeric antigen receptor T-cell therapy for T-cell acute lymphoblastic leukemia.Haematologica · 2024Review
- Article
- Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.Nature communications · 2024Article
- Progress and Pitfalls of Chimeric Antigen Receptor T Cell Immunotherapy against T Cell Malignancies.Transplantation and cellular therapy · 2024Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant T cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR T cells rapidly differentiated into short-lived effector cells. In contrast, 4-1BB costimulation is known to promote development of the central memory subpopulation. Here, we found BB.z CD5 CAR T cells had impaired growth compared with 28.z CD5.CAR T cells, due to increased T-cell-T-cell fratricide. We demonstrate that TRAF signaling from the 4-1BB endodomain upregulated the intercellular adhesion molecule 1, which stabilized the fratricidal immunologic synapse between CD5 CAR T cells. As the surviving BB.z CD5 CAR T cells retained the desired central memory phenotype, we aimed to circumvent the 4-1BB-mediated toxicity using a regulated expression system that reversibly inhibits CAR expression. This system minimized CAR signaling and T-cell fratricide during
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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.