ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.
- A bibliometric review of oncolytic virus research as a novel approach for cancer therapy.Virology journal · 2021Pooled it
- Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Rewiring oncogenic signalling to precision ablation of metastatic cancer.Nature biomedical engineering · 2026Article
- Oncolytic Viruses in Cancer Immunotherapy: From Molecular Engineering to Clinical Translation.Cells · 2026Review
- Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- OV Modulators of the Paediatric Brain TIME: Current Status, Combination Strategies, Limitations and Future Directions.International journal of molecular sciences · 2024Review
- Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell-Based Immunotherapies.Cancer immunology research · 2024Article
- Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.Frontiers in cell and developmental biology · 2024Review
- Breaking the barriers in cancer care: The next generation of herpes simplex virus-based oncolytic immunotherapies for cancer treatment.Molecular therapy oncolytics · 2023Review
- Improved oncolytic activity of a reovirus mutant that displays enhanced virus spread due to reduced cell attachment.Molecular therapy oncolytics · 2023Article
- Therapy with oncolytic viruses: progress and challenges.Nature reviews. Clinical oncology · 2023Review
- The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles.International journal of molecular sciences · 2023Review
- The emerging field of oncolytic virus-based cancer immunotherapy.Trends in cancer · 2023Review
- Clinical advances in oncolytic virotherapy for pediatric brain tumors.Pharmacology & therapeutics · 2022Review
- Infection of non-cancer cells: A barrier or support for oncolytic virotherapy?Molecular therapy oncolytics · 2022Review
- Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy.Frontiers in cellular neuroscience · 2022Review
- Review
- Antiviral antibody responses to systemic administration of an oncolytic RNA virus: the impact of standard concomitant anticancer chemotherapies.Journal for immunotherapy of cancer · 2021Article
- Oncolytic herpes simplex virus infects myeloma cellsMolecular therapy oncolytics · 2021Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeThe purpose of the present study was to investigate whether it is possible to achieve truly systemic delivery of oncolytic reovirus, in immunocompetent hosts, using cyclophosphamide to overcome some of the barriers to effective intratumoral delivery and replication of i.v. injected virus. EXPERIMENTAL
designI.v. delivery of reovirus was combined with different regimens of i.p. administered cyclophosphamide in C57Bl/6 mice bearing established s.c. B16 tumors. Intratumoral viral replication, tumor size, and survival were measured along with levels of neutralizing antibody (NAb) in the blood. Finally, differential toxicities of the virus/cyclophosphamide regimens were monitored through viral replication in systemic organs, survival, and cardiac damage.
resultsRepeated i.v. injection of reovirus was poorly effective at seeding intratumoral viral replication/oncolysis. However, by combining i.v. virus with cyclophosphamide, viral titers of between 10(7) and 10(8) plaque-forming units per milligram were recovered from regressing tumors. Doses of cyclophosphamide that ablated NAb were associated with severe toxicities, characterized by viral replication in systemic organs--toxicities that are mirrored by repeated reovirus injections into B-cell knockout mice. Next, we restructured the dosing of cyclophosphamide and i.v. virus such that a dose of 3 mg cyclophosphamide was administered 24 h before reovirus injection, and this schedule was repeated every 6 days. Using this protocol, high levels of intratumoral viral access and replication ( approximately 10(7) plaque-forming units per milligram tumor) were maintained along with systemically protective levels of NAb and only very mild, non-life-threatening toxicity.
conclusionNAb to oncolytic viruses play a dual role in the context of systemic viral delivery; on one hand, they hinder repeated administration of virus but on the other, they provide an important safety mechanism by which virus released from vigorous intratumoral replication is neutralized before it can disseminate and cause toxicity. These data support the use of cyclophosphamide to modulate, but not ablate, patient NAb, in development of carefully controlled clinical trials of the systemic administration of oncolytic viruses.
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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.