ReviewFrontiers in immunology2026
Gene-based immunotherapy in osteosarcoma: from oncolytic vectors to engineered immune cells.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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0 citing papers in PubMed.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma remains difficult to cure once it metastasizes, recurs, or becomes resistant to chemotherapy. Surgery combined with multi-drug chemotherapy improves outcomes in localized disease, but outcomes for high-risk patients have plateaued, prompting renewed interest in immunotherapy. However, immune checkpoint blockade has limited efficacy in unselected osteosarcoma patients: in SARC028, one objective response was observed among 22 patients with osteosarcoma treated with pembrolizumab. This limited response is consistent with antigen heterogeneity, enrichment of immunosuppressive myeloid populations, insufficient cytotoxic lymphocyte infiltration, matrix-associated immune exclusion, and metastatic immune adaptation. Gene-based immunotherapy offers a complementary strategy. When endogenous immune priming is inadequate, these platforms may initiate, reshape, or amplify antitumor immunity by promoting oncolytic antigen release, local cytokine or chemokine expression, engineered immune-cell recognition, or non-viral delivery of immunomodulatory payloads. This article discusses oncolytic vectors, cytokine-armed vectors, CAR-T and CAR-NK cells, TCR- or neoantigen-directed strategies, and non-viral gene delivery systems as potential approaches for reshaping osteosarcoma immunity. It also examines combination strategies and translational challenges in pediatric and adolescent patients. Beyond summarizing platform-level evidence, we distinguish findings generated directly in osteosarcoma from evidence extrapolated from other tumor types, identify the principal unresolved knowledge gaps for each platform, and summarize the current osteosarcoma-specific clinical trial landscape to clarify the translational maturity of these strategies.
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