ArticleThe Journal of biological chemistry2010
Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01818323 (Phase I Trial), which is not on this map. Cited by 110 papers, 2 of them syntheses that pooled it.
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.
Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- Genetically inducible coordinators of cytokine signaling pathways for interrogating T cell motility.bioRxiv : the preprint server for biology · 2026Article
- Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy.Nature biomedical engineering · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- CAR T-cells for the treatment of CNS malignancies.Frontiers in immunology · 2026Review
- CAR-T cells in solid tumors: Challenges and breakthroughs.Cell reports. Medicine · 2025Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma.Biomarker research · 2025Review
- Revolutionizing Cancer Treatment: Unveiling the Power of CAR T-cell Therapy.Current pharmaceutical design · 2025Review
- GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.Immunotherapy advances · 2025Article
- Chimeric switch and inverted cytokine receptors in T cell therapy: reprogramming T cells to overcome immune suppression in the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Nuclear-Based Labeling of Cellular Immunotherapies: A Simple Protocol for Preclinical Use.Molecular imaging and biology · 2024Article
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: how far are we from a clinical application?Haematologica · 2024Review
- Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors.Medical oncology (Northwood, London, England) · 2024Review
- CAR-T cell therapy in advanced thyroid cancer: from basic to clinical.Frontiers in immunology · 2024Review
- Arming CAR-T cells with cytokines and more: Innovations in the fourth-generation CAR-T development.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Polyclonal T-cells can be directed against cancer using transmembrane fusion molecules known as chimeric antigen receptors (CARs). Although preclinical studies have provided encouragement, pioneering clinical trials using CAR-based immunotherapy have been disappointing. Key obstacles are the need for robust expansion ex vivo followed by sustained survival of infused T-cells in patients. To address this, we have developed a system to achieve selective proliferation of CAR(+) T-cells using IL-4, a cytokine with several pathophysiologic and therapeutic links to cancer. A chimeric cytokine receptor (4alphabeta) was engineered by fusion of the IL-4 receptor alpha (IL-4Ralpha) ectodomain to the beta(c) subunit, used by IL-2 and IL-15. Addition of IL-4 to T-cells that express 4alphabeta resulted in STAT3/STAT5/ERK phosphorylation and exponential proliferation, mimicking the actions of IL-2. Using receptor-selective IL-4 muteins, partnering of 4alphabeta with gamma(c) was implicated in signal delivery. Next, human T-cells were engineered to co-express 4alphabeta with a CAR specific for tumor-associated MUC1. These T-cells exhibited an unprecedented capacity to elicit repeated destruction of MUC1-expressing tumor cultures and expanded through several logs in vitro. Despite prolonged culture in IL-4, T-cells retained specificity for target antigen, type 1 polarity, and cytokine dependence. Similar findings were observed using CARs directed against two additional tumor-associated targets, demonstrating generality of application. Furthermore, this system allows rapid ex vivo expansion and enrichment of engineered T-cells from small blood volumes, under GMP-compliant conditions. Together, these findings provide proof of principle for the development of IL-4-enhanced T-cell immunotherapy of cancer.
Indexed as
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.