ArticleCancer immunology research2015
Individual Motile CD4(+) T Cells Can Participate in Efficient Multikilling through Conjugation to Multiple Tumor Cells.
Article in Cancer immunology research, 2015. 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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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
72 citing papers in PubMed, 102 citations in OpenAlex.
- Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.Cancer cell · 2026Article
- Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Safety and clinical outcomes of a first-in-human trial of point-of-care manufactured trispecific CAR T cells targeting CD19, CD20, and CD22.Research square · 2026Article
- A novel pseudotype derived of the canine distemper virus for adapter-mediated lentiviral transductionMolecular therapy. Methods & clinical development · 2025Article
- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Depletion of Tregs from CD4The FEBS journal · 2025Article
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- ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis.Journal for immunotherapy of cancer · 2024Article
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- PostFocus: automated selective post-acquisition high-throughput focus restoration using diffusion model for label-free time-lapse microscopy.Bioinformatics (Oxford, England) · 2024Article
- Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling.Nature cancer · 2024Article
- The role of CD4Translational cancer research · 2024Article
- Targeting senescent cells with NKG2D-CAR T cells.Cell death discovery · 2024Article
- Challenges and strategies associated with CAR-T cell therapy in blood malignancies.Experimental hematology & oncology · 2024Review
- Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy.Frontiers in molecular medicine · 2024Review
- Automated detection of apoptotic bodies and cells in label-free time-lapse high-throughput video microscopy using deep convolutional neural networks.Bioinformatics (Oxford, England) · 2023Article
- Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4Nature cancer · 2023Article
- CAR T-cell behavior and function revealed by real-time imaging.Seminars in immunopathology · 2023Review
- Microraft arrays for serial-killer CD19 chimeric antigen receptor T cells and single cell isolation.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023Article
- Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
T cells genetically modified to express a CD19-specific chimeric antigen receptor (CAR) for the investigational treatment of B-cell malignancies comprise a heterogeneous population, and their ability to persist and participate in serial killing of tumor cells is a predictor of therapeutic success. We implemented Timelapse Imaging Microscopy in Nanowell Grids (TIMING) to provide direct evidence that CD4(+)CAR(+) T cells (CAR4 cells) can engage in multikilling via simultaneous conjugation to multiple tumor cells. Comparisons of the CAR4 cells and CD8(+)CAR(+) T cells (CAR8 cells) demonstrate that, although CAR4 cells can participate in killing and multikilling, they do so at slower rates, likely due to the lower granzyme B content. Significantly, in both sets of T cells, a minor subpopulation of individual T cells identified by their high motility demonstrated efficient killing of single tumor cells. A comparison of the multikiller and single-killer CAR(+) T cells revealed that the propensity and kinetics of T-cell apoptosis were modulated by the number of functional conjugations. T cells underwent rapid apoptosis, and at higher frequencies, when conjugated to single tumor cells in isolation, and this effect was more pronounced on CAR8 cells. Our results suggest that the ability of CAR(+) T cells to participate in multikilling should be evaluated in the context of their ability to resist activation-induced cell death. We anticipate that TIMING may be used to rapidly determine the potency of T-cell populations and may facilitate the design and manufacture of next-generation CAR(+) T cells with improved efficacy.
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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.