ArticleMolecular therapy. Oncology2024
Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.
Article in Molecular therapy. Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed.
- 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
- Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026Review
- Oncolytic Maraba Virus MG1 Mediates Direct and Natural Killer Cell-Dependent Lysis of Ewing Sarcoma.Cancers · 2025Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Exploiting divergent mechanisms of trabectedin for bone tumors.Molecular therapy. Oncology · 2025Article
- Trabectedin Enhances the Antitumor Effects of IL-12 in Triple-Negative Breast Cancer.Cancer immunology research · 2025Article
- Immunotherapy for high-grade endometrial stromal sarcoma: a narrative review bridging molecular insights to clinical translation.Frontiers in immunology · 2025Review
- Oncolytic virus therapy for osteosarcoma: mechanisms, opportunities, and challenges.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing infiltrating immunosuppressive CD4 T and myeloid cells and stimulating granzyme expression in infiltrating T and natural killer cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.
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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 Socratic graph.