ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.
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Who cites it
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
- The efficacy of chimeric antigen receptor (CAR) immunotherapy in animal models for solid tumors: A systematic review and meta-analysis.PloS one · 2017Pooled it
- Autologous multiantigen-targeted T cell therapy for pancreatic cancer: a phase 1/2 trial.Nature medicine · 2026Trial
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026Review
- Engineered macrophages with IL-10-TLR9 signal switch receptors for reprogramming tumor microenvironment and enhancing antitumor immunity.Experimental & molecular medicine · 2026Article
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- Precise control of switchable chimeric antigen receptor T cells allows enhanced safety and less T cell exhaustion.Journal of translational medicine · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Antigen-IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα.Journal for immunotherapy of cancer · 2026Article
- Hypoxic-immune axis orchestrates metastatic dissemination via HIF isoform imbalance in pancreatic neuroendocrine tumors.iScience · 2026Article
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Transcriptional dynamics of CD8Molecular cancer · 2025Article
- Precise Control of Switchable Chimeric Antigen Receptor T Cells Allows Enhanced Safety and Less T Cell Exhaustion.bioRxiv : the preprint server for biology · 2025Article
- Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia.Nature biomedical engineering · 2025Article
- Cytokine Engineering in CAR-T Cell Therapy: Next-Generation Strategies.Immune network · 2025Review
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives.Biomedicines · 2025Review
129 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression of chimeric antigen receptors (CARs) has produced tumor responses, even in patients with refractory diseases. To target pancreatic cancer, we generated CAR T cells directed against prostate stem cell antigen (PSCA) and demonstrated specific tumor lysis. However, pancreatic tumors employ immune evasion strategies such as the production of inhibitory cytokines, which limit CAR T cell persistence and function. Thus, to protect our cells from the immunosuppressive cytokine IL-4, we generated an inverted cytokine receptor in which the IL-4 receptor exodomain was fused to the IL-7 receptor endodomain (4/7 ICR). Transgenic expression of this molecule in CAR-PSCA T cells should invert the inhibitory effects of tumor-derived IL-4 and instead promote T cell proliferation. We now demonstrate the suppressed activity of CAR T cells in tumor-milieu conditions and the ability of CAR/ICR T cells to thrive in an IL-4-rich microenvironment, resulting in enhanced antitumor activity. Importantly, CAR/ICR T cells remained both antigen and cytokine dependent. These findings support the benefit of combining the 4/7 ICR with CAR-PSCA to treat pancreatic cancer, a PSCA-expressing tumor characterized by a dense immunosuppressive environment rich in IL-4.
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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.