ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Regulating cytokine function enhances safety and activity of genetic cancer therapies.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 28 citations in OpenAlex.
- Oncolytic viruses as anticancer agents: clinical progress and remaining challenges.Lancet (London, England) · 2025Review
- Therapy of 4T1 breast cancer in mice with Vaccinia virus encoding tumor-associated antigen epitopes and mouse IL2 cytokine.Frontiers in immunology · 2025Article
- The Future of Interventions for Stage IV Colorectal Cancers.Clinics in colon and rectal surgery · 2024Review
- Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy.Human gene therapy · 2023Review
- Oncolytic Vaccinia Virus Gene Modification and Cytokine Expression Effects on Tumor Infection, Immune Response, and Killing.Molecular cancer therapeutics · 2021Article
- Review
- Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors.Science translational medicine · 2020Article
- CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency.Journal for immunotherapy of cancer · 2020Article
- Oncolytic Virus-Based Cytokine Expression to Improve Immune Activity in Brain and Solid Tumors.Molecular therapy oncolytics · 2019Review
- Delivering safer immunotherapies for cancer.Advanced drug delivery reviews · 2017Review
- Oncolytic Virotherapy and the Tumor Microenvironment.Advances in experimental medicine and biology · 2017Review
- Targeting Melanoma with Cancer-Killing Viruses.The open virology journal · 2017Article
- Article
- Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens through Oncolytic Vaccines.Frontiers in immunology · 2017Review
- Oncolytic Virus-Mediated Targeting of PGE2 in the Tumor Alters the Immune Status and Sensitizes Established and Resistant Tumors to Immunotherapy.Cancer cell · 2016Article
- Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by Viral Cancer Therapies.Cell reports · 2016Article
- Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy.Oncolytic virotherapy · 2015Review
- Immunotherapeutic potential of oncolytic vaccinia virus.Frontiers in oncology · 2014Review
- Arming viruses in multi-mechanistic oncolytic viral therapy: current research and future developments, with emphasis on poxviruses.Oncolytic virotherapy · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Genetic therapies, including transfected immune cells and viral vectors, continue to show clinical responses as systemically deliverable and targeted therapeutics, with the first such approaches having been approved for cancer treatment. The majority of these employ cytokine transgenes. However, expression of cytokines early after systemic delivery can result in increased toxicity and nonspecific induction of the immune response. In addition, premature immune-mediated clearance of the therapy may result, especially for viral-based approaches. Here, it was initially verified that cytokine (interleukin (IL)2) or chemokine (CCL5) expression from a systemically delivered oncolytic virus resulted in reduced oncolytic activity and suboptimal immune activation, while IL2 also resulted in increased toxicity. However, all these limitations could be overcome through incorporation of exogenous regulation of cytokine or chemokine transgene function through fusion of a small and externally controllable destabilizing domain to the protein of interest. Regulation allowed an initial phase without cytokine function, permitting enhanced delivery and oncolytic activity before activation of cytokine function and a subsequent phase of enhanced and tumor-targeted immunotherapeutic activity. As a result of this exogenous regulation of cytokine function, both oncolytic and immune-mediated mechanisms of action were optimized, greatly enhancing therapeutic activity, while toxicity was significantly reduced.
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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.