Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans |
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Authors: | Breitbach Caroline J Burke James Jonker Derek Stephenson Joe Haas Andrew R Chow Laura Q M Nieva Jorge Hwang Tae-Ho Moon Anne Patt Richard Pelusio Adina Le Boeuf Fabrice Burns Joe Evgin Laura De Silva Naomi Cvancic Sara Robertson Terri Je Ji-Eun Lee Yeon-Sook Parato Kelley Diallo Jean-Simon Fenster Aaron Daneshmand Manijeh Bell John C Kirn David H |
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Institution: | Jennerex Inc., 450 Sansome Street, 16th floor, San Francisco, California 94111, USA. |
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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. |
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