ArticleBlood2020
Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial.Journal for immunotherapy of cancer · 2024Trial
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Dysregulation of the urea cycle - potential targets for treatment and diagnosis in prostate cancer.Expert reviews in molecular medicine · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Review
- Metabolic reprogramming of CAR-T cells: a multi-pronged strategy to conquer the immunosuppressive tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
73 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
16 authors at 2 institutions in 1 country.
Funding
Abstract
Hematological and solid cancers catabolize the semiessential amino acid arginine to drive cell proliferation. However, the resulting low arginine microenvironment also impairs chimeric antigen receptor T cells (CAR-T) cell proliferation, limiting their efficacy in clinical trials against hematological and solid malignancies. T cells are susceptible to the low arginine microenvironment because of the low expression of the arginine resynthesis enzymes argininosuccinate synthase (ASS) and ornithine transcarbamylase (OTC). We demonstrate that T cells can be reengineered to express functional ASS or OTC enzymes, in concert with different chimeric antigen receptors. Enzyme modifications increase CAR-T cell proliferation, with no loss of CAR cytotoxicity or increased exhaustion. In vivo, enzyme-modified CAR-T cells lead to enhanced clearance of leukemia or solid tumor burden, providing the first metabolic modification to enhance CAR-T cell therapies.
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.