ArticlePediatric blood & cancer2014
Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis.
Article in Pediatric blood & cancer, 2014. 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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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
28 citing papers in PubMed, 45 citations in OpenAlex.
- Primary metastatic osteosarcoma: results of a prospective study in children given chemotherapy and interleukin-2.Medical oncology (Northwood, London, England) · 2017Trial
- Intratumoral TIGIT blockade augments antitumor responses and bypasses increased functionality of peripheral TIGIT+ NK cells in mouse and human models of bone and soft tissue sarcoma.Journal for immunotherapy of cancer · 2026Article
- Precision nanomedicine for lung metastatic osteosarcoma: challenges, therapeutic strategies, and perspectives.Materials today. Bio · 2026Review
- Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy.Frontiers in immunology · 2026Review
- Development and evaluation of an inhalable nanoemulsion system for enhancing NK cell function against osteosarcoma pulmonary metastases.Frontiers in immunology · 2026Article
- Targeting the osteosarcoma immune microenvironment for improved immunotherapy and translational applications.Discover oncology · 2025Review
- Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma.Bone research · 2024Article
- Interleukin-2 and regulatory T cells in rheumatic diseases.Nature reviews. Rheumatology · 2021Review
- Advancing therapy for osteosarcoma.Nature reviews. Clinical oncology · 2021Review
- Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.International journal of cancer · 2021Article
- Prospects for NK Cell Therapy of Sarcoma.Cancers · 2020Review
- Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.African health sciences · 2020Article
- Natural Killer Cell Immunotherapy for Osteosarcoma.Advances in experimental medicine and biology · 2020Review
- Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases.Cancer medicine · 2018Article
- Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment.Oncotarget · 2017Review
- Osteosarcoma Overview.Rheumatology and therapy · 2017Review
- Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.Translational oncology · 2017Article
- Interleukin-2: Old and New Approaches to Enhance Immune-Therapeutic Efficacy.Advances in experimental medicine and biology · 2017Review
- Immune Therapy for Sarcomas.Advances in experimental medicine and biology · 2017Review
- Strategies and developments of immunotherapies in osteosarcoma.Oncology letters · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSurvival of patients with osteosarcoma lung metastases has not improved in 20 years. We evaluated the efficacy of combining natural killer (NK) cells with aerosol interleukin-2 (IL-2) to achieve organ-specific NK cell migration and expansion in the metastatic organ, and to decrease toxicity associated with systemic IL-2. PROCEDURE: Five human osteosarcoma cell lines and 103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand (NKG2DL) expression. Therapeutic efficacy of aerosol IL-2 + NK cells was evaluated in vivo compared with aerosol IL-2 alone and NK cells without aerosol IL-2.
resultsOsteosarcoma cell lines and patient samples expressed various levels of NKG2DL. NK-mediated killing was NKG2DL-dependent and correlated with expression levels. Aerosol IL-2 increased NK cell numbers in the lung and within metastatic nodules but not in other organs. Therapeutic efficacy, as judged by tumor number, size, and quantification of apoptosis, was also increased compared with NK cells or aerosol IL-2 alone. There were no IL-2-associated systemic toxicities.
conclusionAerosol IL-2 augmented the efficacy of NK cell therapy against osteosarcoma lung metastasis, without inducing systemic toxicity. Our data suggest that lung-targeted IL-2 delivery circumvents toxicities induced by systemic administration. Combining aerosol IL-2 with NK cell infusions, may be a potential new therapeutic approach for patients with osteosarcoma lung metastasis.
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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.