ArticleNature medicine2015
Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 511 papers.
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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.
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Who cites it
511 citing papers in PubMed, 765 citations in OpenAlex.
- Innovations and emerging trends in adoptive cell therapies for solid tumors: engineering strategies and clinical translation.Experimental hematology & oncology · 2026Review
- Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.Science advances · 2026Article
- Engineering CAR-T cell therapies for digestive tract cancer: advances, challenges, and strategies to overcome tumor heterogeneity and immunosuppressive barriers.Neoplasia (New York, N.Y.) · 2026Review
- Enzyme-mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors.Bioengineering & translational medicine · 2026Review
- Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx.bioRxiv : the preprint server for biology · 2026Article
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Microfluidic Cytotongue system enables early, label-free detection of CAR-T-induced mechanical softening in tumor spheroids.Microsystems & nanoengineering · 2026Article
- Microfluidic perspectives on chimeric antigen receptor T-cell migration in solid tumours: highlighting physical confinement as a key barrier.Molecular systems design & engineering · 2026Review
- Cancer Immunotherapy: Therapeutic Limitations and Next-Generation Precision Strategies.Immune network · 2026Review
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.Cancer cell international · 2026Review
- Low-dose docetaxel reprograms CAR T cells for enhanced solid tumor immunity.Journal of experimental & clinical cancer research : CR · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- A bibliometric and visualized analysis of CAR-T or TCR-T in solid tumor (from 2015 to 2024).Discover oncology · 2026Article
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Focused ultrasound for enhancing cell-based immunotherapies in neuro-oncology.Neuro-oncology advances · 2026Review
451 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking therapeutic effects in solid tumors than in lymphoid malignancies. Although active tumor-mediated immunosuppression may have a role in limiting the efficacy of CAR-T cells, functional changes in T lymphocytes after their ex vivo manipulation may also account for the reduced ability of cultured CAR-T cells to penetrate stroma-rich solid tumors compared with lymphoid tissues. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE), which degrades heparan sulfate proteoglycans, the main components of ECM. We found that HPSE mRNA is downregulated in in vitro-expanded T cells, which may be a consequence of p53 (officially known as TP53, encoding tumor protein 53) binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed their improved capacity to degrade the ECM, which promoted tumor T cell infiltration and antitumor activity. The use of this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors.
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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.