ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Clinical Application of Oncolytic Viruses: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells.Journal of translational medicine · 2019Trial
- Neural stem cell delivery of oncolytic CRAd-S-pk7 immunotherapy for stage 3 ovarian cancer: Dose-regimen studies.Molecular therapy. Oncology · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- The emerging role of oncolytic virotherapy in genitourinary malignancies.Frontiers in cell and developmental biology · 2026Review
- Recent advances in oncolytic virus combined immunotherapy in tumor treatment.Genes & diseases · 2025Review
- Vaccinia Virus-A Swiss Army Knife Against Cancer.Cancers · 2025Review
- Advances of oncolytic vaccinia viruses armed with interleukin in tumor therapy.Frontiers in oncology · 2025Review
- Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.Nature protocols · 2024Review
- Recent progress in combination therapy of oncolytic vaccinia virus.Frontiers in immunology · 2024Review
- Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.Journal of translational medicine · 2023Review
- Generation of novel oncolytic vaccinia virus with improved intravenous efficacy through protection against complement-mediated lysis and evasion of neutralization by vaccinia virus-specific antibodies.Journal for immunotherapy of cancer · 2023Article
- Oncolytic vaccinia virus and cancer immunotherapy.Frontiers in immunology · 2023Review
- Development of Allogeneic Stem Cell-Based Platform for Delivery and Potentiation of Oncolytic Virotherapy.Cancers · 2022Article
- pH Sensitive Erythrocyte-Derived Membrane for Acute Systemic Retention and Increased Infectivity of Coated Oncolytic Vaccinia Virus.Pharmaceutics · 2022Article
- Cutting both ways: the innate immune response to oncolytic virotherapy.Cancer gene therapy · 2022Review
- A systematic analysis on the clinical safety and efficacy of onco-virotherapy.Molecular therapy oncolytics · 2021Article
- Review
- A sensitive and reproducible cell-based assay via secNanoLuc to detect neutralizing antibody against adeno-associated virus vector capsid.Molecular therapy. Methods & clinical development · 2021Article
- Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus.Molecular therapy oncolytics · 2021Article
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 3 countries.
Funding
Abstract
Oncolytic viruses (OVs) have shown promising clinical activity when administered by direct intratumoral injection. However, natural barriers in the blood, including antibodies and complement, are likely to limit the ability to repeatedly administer OVs by the intravenous route. We demonstrate here that for a prototype of the clinical vaccinia virus based product Pexa-Vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune virus treated cancer patients, is strictly dependent on the activation of complement. In immunized rats, complement depletion stabilized vaccinia virus in the blood and led to improved delivery to tumors. Complement depletion also enhanced tumor infection when virus was directly injected into tumors in immunized animals. The feasibility and safety of using a complement inhibitor, CP40, in combination with vaccinia virus was tested in cynomolgus macaques. CP40 pretreatment elicited an average 10-fold increase in infectious titer in the blood early after the infusion and prolonged the time during which infectious virus was detectable in the blood of animals with preexisting immunity. Capitalizing on the complement dependence of antivaccinia antibody with adjunct complement inhibitors may increase the infectious dose of oncolytic vaccinia virus delivered to tumors in virus in immune hosts.
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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.