ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Selectivity of oncolytic viral replication prevents antiviral immune response and toxicity, but does not improve antitumoral immunity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Construction and application of adenoviral vectors.Molecular therapy. Nucleic acids · 2023Review
- Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?Frontiers in oncology · 2021Review
- Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model.Journal of medical virology · 2018Article
- Oncolytic viruses: adenoviruses.Virus genes · 2017Review
- Oncolytic Virotherapy and the Tumor Microenvironment.Advances in experimental medicine and biology · 2017Review
- Showing the Way: Oncolytic Adenoviruses as Chaperones of Immunostimulatory Adjuncts.Biomedicines · 2016Review
- Oncolytic viruses as immunotherapy: progress and remaining challenges.OncoTargets and therapy · 2016Review
- Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Oncolytic viruses as therapeutic cancer vaccines.Molecular cancer · 2013Review
- Meganuclease-mediated virus self-cleavage facilitates tumor-specific virus replication.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Ad3-hTERT-E1A, a fully serotype 3 oncolytic adenovirus, in patients with chemotherapy refractory cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Replicating viral vectors for cancer therapy: strategies to synergize with host immune responses.Microbial biotechnology · 2012Review
- Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice.The Journal of clinical investigation · 2011Article
- Thunder and lightning: immunotherapy and oncolytic viruses collide.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Review
- A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.PLoS computational biology · 2011Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncolytic infection elicits antitumoral immunity, but the impact of tumor-selective replication on the balance between antiviral and antitumoral immune responses has not yet been investigated. To address this question, we constructed the highly tumor-selective adenovirus Ad-p53T whose replication in target tumor cells is governed by aberrant telomerase activity and transcriptional p53 dysfunction. Telomerase-dependent or nonselective adenoviruses were constructed as isogenic controls. Following infection of mice with the nonselective adenovirus, viral DNA and mRNA levels correlated with strong stimulation of innate immune response genes and severe liver toxicity, whereas telomerase-/p53-specific replication did not trigger innate immunity and prevented liver damage. Compared to telomerase-dependent or unselective viral replication, telomerase-/p53-specific virotherapy significantly decreased antiviral CD8-specific immune responses and antiviral cytotoxicity in vivo. Consistent with our hypothesis, telomerase-selective replication led to intermediate results in these experiments. Remarkably, all viruses efficiently lysed tumors and induced a therapeutically effective tumor-directed CD8 cytotoxicity. In immunocompetent mice with extended lung metastases burden, treatment of subcutaneous primary tumors with Ad-p53T significantly prolonged survival by inhibition of lung metastases, whereas unselective viral replication resulted in death by liver failure. In summary, the degree of tumor selectivity of viral replication marginally influences antitumoral immune responses, but is a major determinant of antivector immunity and systemic toxicity.
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