ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Adipocytes: A Novel Target for IL-15/IL-15Rα Cancer Gene Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Adipocytes in cancer a metabolic paradox and the dawn of novel therapeutics.Discover oncology · 2026Review
- Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity.Molecular therapy. Advances · 2026Article
- Unraveling vascular mechanisms in melanoma: roles of angiogenesis and vasculogenic mimicry in tumor progression and therapeutic resistance.Cancer biology & medicine · 2025Review
- Integrin CD103 expression in naive CD8Immunity · 2025Article
- Subcutaneous administration of adipose-tropic gene therapy for congenital leptin deficiency.Research square · 2025Article
- Precision medicine: toward restoring fat with gene therapy in inherited lipodystrophy.Gene therapy · 2024Article
- Article
- Physical Activity Decreases Inflammation and Delays the Development of Obesity-Associated Pancreatic Ductal Adenocarcinoma.Cancer research · 2024Article
- Molecular Imaging of Melanoma VEGF-expressing Tumors through [Anti-cancer agents in medicinal chemistry · 2024Article
- Targeting adipocyte-immune cell crosstalk to control breast cancer progression.Journal of cancer research and clinical oncology · 2023Review
- Adipocyte CD1d Gene Transfer Induces T Cell Expansion and Adipocyte Inflammation in CD1d Knockout Mice.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The role of angiogenesis in melanoma: Clinical treatments and future expectations.Frontiers in pharmacology · 2022Review
- Exercise-induced IL-15 acted as a positive prognostic implication and tumor-suppressed role in pan-cancer.Frontiers in pharmacology · 2022Article
- Spatiotemporally co-delivery of triple therapeutic drugs via HA-coating nanosystems for enhanced immunotherapy.Asian journal of pharmaceutical sciences · 2021Article
- Environmental activation of a hypothalamic BDNF-adipocyte IL-15 axis regulates adipose-natural killer cells.Brain, behavior, and immunity · 2021Article
- Visceral adipose tissue-directed FGF21 gene therapy improves metabolic and immune health in BTBR mice.Molecular therapy. Methods & clinical development · 2021Article
- Enriched environment enhances NK cell maturation through hypothalamic BDNF in male mice.European journal of immunology · 2021Article
- Innate Immune System Orchestrates Metabolic Homeostasis and Dysfunction in Visceral Adipose Tissue During Obesity.Frontiers in immunology · 2021Review
- Enhancing Effects of Environmental Enrichment on the Functions of Natural Killer Cells in Mice.Frontiers in immunology · 2021Review
- Adipose Tissue: An Emerging Target for Adeno-associated Viral Vectors.Molecular therapy. Methods & clinical development · 2020Review
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10 authors at 3 institutions in 1 country.
Funding
Abstract
IL-15 is a proinflammatory cytokine that plays an essential role in the development and activation of natural killer (NK) cells. Adipose tissue acts as an endocrine organ that secretes cytokines and is an important reservoir for lymphocytes. We hypothesized that activation of the IL-15 signaling in adipose tissue will activate and expand the NK cell population and control tumor growth. We recently developed an adipocyte-targeting recombinant adeno-associated viral (rAAV) vector with minimal off-target transgene expression in the liver. Here, we used this rAAV system to deliver an IL-15/IL-15Rα complex to the abdominal fat by intraperitoneal (i.p.) injection. Adipose IL-15/IL-15Rα complex gene transfer led to the expansion of NK cells in the adipose tissue and spleen in normal mice without notable side effects. The i.p. injection of rAAV-IL-15/IL-15Rα complex significantly suppressed the growth of Lewis lung carcinoma implanted subcutaneously and exerted a significant survival advantage in a B16-F10 melanoma metastasis model. The antitumor effects were associated with the expansion of the NK cells in the blood, spleen, abdominal fat, and tumor, as well as the enhancement of NK cell maturity. Our proof-of-concept preclinical studies demonstrate the safety and efficacy of the adipocyte-specific IL-15/IL-15Rα complex vector as a novel cancer immune gene therapy.
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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.