Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans
- PMID: 21886163
- DOI: 10.1038/nature10358
Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans
Abstract
The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.
Comment in
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Cancer: Tumour-fighting virus homes in.Nature. 2011 Aug 31;477(7362):40-1. doi: 10.1038/477040a. Nature. 2011. PMID: 21886153 No abstract available.
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Immunotherapy: Seek and destroy: oncolytic virus shows promise in phase I trial.Nat Rev Clin Oncol. 2011 Sep 20;8(11):630. doi: 10.1038/nrclinonc.2011.143. Nat Rev Clin Oncol. 2011. PMID: 21931354 No abstract available.
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Cancer: Oncolytic poxvirus homes in on cancer cells.Nat Rev Drug Discov. 2011 Oct 31;10(11):814. doi: 10.1038/nrd3589. Nat Rev Drug Discov. 2011. PMID: 22037035 No abstract available.
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