ArticleOncoimmunology2023
Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer.
Article in Oncoimmunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Next-generation oncolytic virotherapy for lung cancer: bridging innovative vector engineering with clinical immunotherapy.Translational lung cancer research · 2026Review
- Oncolytic viruses in lung cancer: mechanisms of action and research progress.Frontiers in microbiology · 2026Review
- Recent advances in oncolytic virus combined immunotherapy in tumor treatment.Genes & diseases · 2025Review
- Dual blockade of TNFR2 and CD47 reshape tumor immune microenvironment and improve antitumor effects in colorectal cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Combination of low-intensity pulsed ultrasound irradiating immune organs with immune checkpoint blockade augments systemic anti-tumor immunity on low tumor burden 4T-1 breast cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Four-gene Prognostic Signature and Risk of Brain Metastasis of Lung Adenocarcinoma.Molecular carcinogenesis · 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
- KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis.Molecular therapy. Oncology · 2025Article
- 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
- The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial.Nature communications · 2025Article
- Immunotherapy in Oncogene-Addicted NSCLC: Evidence and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- The Emerging Mechanisms and Therapeutic Potentials of Dendritic Cells in NSCLC.Journal of inflammation research · 2025Review
- Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms.Frontiers in immunology · 2025Review
- An Engineered Self-biomineralized Oncolytic Adenovirus Induces Effective Antitumor Immunity and Synergizes With Immune Checkpoint Blockade.Cancer immunology research · 2024Article
- Safety, Efficacy, and Biological Data of T-Cell-Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Review
- Advancing non-small cell lung cancer treatment: the power of combination immunotherapies.Frontiers in immunology · 2024Review
- Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.
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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.