ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Ad3-hTERT-E1A, a fully serotype 3 oncolytic adenovirus, in patients with chemotherapy refractory cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 86 citations in OpenAlex.
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- Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.Nature protocols · 2024Review
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- Oncolytic Adenovirus for the Targeting of Paclitaxel-Resistant Breast Cancer Stem Cells.Viruses · 2024Article
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- Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.Engineering microbiology · 2024Review
- Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.Viruses · 2023Review
- Toward the understanding of DSG2 and CD46 interaction with HAdV-11 fiber, a super-complex analysis.Journal of virology · 2023Article
- Adenovirus as a Vector and Oncolytic Virus.Current issues in molecular biology · 2023Review
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- In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4.Blood advances · 2022Article
- Oncolytic adenovirus decreases the proportion of TIM-3Journal for immunotherapy of cancer · 2022Article
- Ad5/3 is able to avoid neutralization by binding to erythrocytes and lymphocytes.Cancer gene therapy · 2021Article
- Oncolytic Adenovirus Type 3 Coding for CD40L Facilitates Dendritic Cell Therapy of Prostate Cancer in Humanized Mice and Patient Samples.Human gene therapy · 2021Article
- Oncolytic Adenovirus: Prospects for Cancer Immunotherapy.Frontiers in microbiology · 2021Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Twenty-five patients with chemotherapy refractory cancer were treated with a fully serotype 3-based oncolytic adenovirus Ad3-hTERT-E1A. In mice, Ad3 induced higher amounts of cytokines but less liver damage than Ad5 or Ad5/3. In humans, the only grade 3 adverse reactions were self-limiting cytopenias and generally the safety profile resembled Ad5-based oncolytic viruses. Patients that had been previously treated with Ad5 viruses presented longer lasting lymphocytopenia but no median increase in Ad3-specific T-cells in blood, suggesting immunological activity against antigens other than Ad3 hexon. Frequent alterations in antitumor T-cells in blood were seen regardless of previous virus exposure. Neutralizing antibodies against Ad3 increased in all patients, whereas Ad5 neutralizing antibodies remained stable. Treatment with Ad3-hTERT-E1A resulted in re-emergence of Ad5 viruses from previous treatments into blood and vice versa. Signs of possible efficacy were seen in 11/15 (73%) patients evaluable for tumor markers, four of which were treated only intravenously. Particularly promising results were seen in breast cancer patients and especially those receiving concomitant trastuzumab. Taken together, Ad3-hTERT-E1A seems safe for further clinical testing or development of armed versions. It offers an immunologically attractive alternative, with possible pharmacodynamic differences and a different receptor compared to Ad5.
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