ArticleJournal for immunotherapy of cancer2020
Oncolytic adenovirus shapes the ovarian tumor microenvironment for potent tumor-infiltrating lymphocyte tumor reactivity.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Recent advances in oncolytic virus combined immunotherapy in tumor treatment.Genes & diseases · 2025Review
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.Molecular cancer · 2025Review
- Tumor Microenvironment in Melanoma-Characteristic and Clinical Implications.International journal of molecular sciences · 2025Review
- Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma.Molecular therapy. Oncology · 2025Article
- Single-cell profiling of peripheral blood mononuclear cells from patients treated with oncolytic adenovirus TILT-123 reveals baseline immune status as a predictor of therapy outcomes.Cancer gene therapy · 2025Article
- Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer.Vaccines · 2025Review
- In situ blockade of TNF-TNFR2 axis via oncolytic adenovirus improves antitumor efficacy in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review.Pathogens (Basel, Switzerland) · 2025Review
- Oncolytic virus encoding 4-1BBL and IL15 enhances the efficacy of tumor-infiltrating lymphocyte adoptive therapy in HCC.Cancer gene therapy · 2025Article
- Developing innovative strategies of tumor‑infiltrating lymphocyte therapy for tumor treatment.Oncology reports · 2024Review
- Sindbis Virus Vaccine Platform: A Promising Oncolytic Virus-Mediated Approach for Ovarian Cancer Treatment.International journal of molecular sciences · 2024Review
- Personalizing Oncolytic Immunovirotherapy Approaches.Molecular diagnosis & therapy · 2024Article
- The investigation of oncolytic viruses in the field of cancer therapy.Frontiers in oncology · 2024Review
- Boosting cytotoxicity of adoptive allogeneic NK cell therapy with an oncolytic adenovirus encoding a human vIL-2 cytokine for the treatment of human ovarian cancer.Cancer gene therapy · 2023Article
- Improving the cytotoxic response of tumor-infiltrating lymphocytes towards advanced stage ovarian cancer with an oncolytic adenovirus expressing a human vIL-2 cytokine.Cancer gene therapy · 2023Article
- Recombinant oncolytic adenovirus armed with CCL5, IL-12, and IFN-γ promotes CAR-T infiltration and proliferation in vivo to eradicate local and distal tumors.Cell death discovery · 2023Article
- Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy.Human gene therapy · 2023Review
- Adenovirus as a Vector and Oncolytic Virus.Current issues in molecular biology · 2023Review
Corrections and comments
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Authors and funding
12 authors.
Funding
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Abstract
backgroundOvarian cancers often contain significant numbers of tumor-infiltrating lymphocytes (TILs) that can be readily harnessed for adoptive T-cell therapy (ACT). However, the immunosuppressive ovarian tumor microenvironment and lack of tumor reactivity in TILs can limit the effectiveness of the therapy. We hypothesized that by using an oncolytic adenovirus (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) to deliver tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2), we could counteract immunosuppression, and enhance antitumor TIL responses in ovarian cancer (OVCA).
methodsWe established ex vivo tumor cultures freshly derived from patients with advanced OVCA and evaluated the effects of Ad5/3-E2F-D24-hTNFa-IRES-hIL2 or Ad5/3-E2F-D24 (the control virus without TNFa and IL-2) on TILs, cytokine response and tumor viability. Tumor reactivity was assessed by determining interferon gamma (IFNg) response of clinically relevant TILs towards autologous T-cell-depleted ex vivo tumor cultures pretreated with or without the aforementioned oncolytic adenoviruses.
resultsTreatment of ex vivo tumor cultures with Ad5/3-E2F-D24-hTNFa-IRES-hIL2 caused a substantial rise in proinflammatory signals: increased secretion of IFNg, CXCL10, TNFa and IL-2, and concomitant activation of CD4+ and CD8+ TILs. Potent tumor reactivity was seen, as clinically relevant TIL secreted high levels of IFNg in response to autologous T-cell-depleted ovarian ex vivo tumor cultures treated with Ad5/3-E2F-D24-hTNFa-IRES-hIL2. This phenomenon was independent of PD-L1 expression in tumor cells, a factor that determined the variability of IFNg responses seen in different patient samples.
conclusionsOverall, oncolytic adenovirus Ad5/3-E2F-D24-hTNFa-IRES-hIL2 was able to rewire the ovarian tumor microenvironment to accommodate heightened antitumor TIL reactivity. Such effects may improve the clinical effectiveness of ACT with TILs in patients with advanced OVCA.
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