RadMD Principal publishes in Nature

RadMD Principal, Richard Patt, MD was recently published in Nature magazine. The article entitled "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans" was published in September 2011. 


Caroline J. Breitbach1, James Burke2{, Derek Jonker3,4, Joe Stephenson5, Andrew R. Haas6, Laura Q. M. Chow3,4, Jorge Nieva2, Tae-Ho Hwang7, Anne Moon1, Richard Patt8, Adina Pelusio1, Fabrice Le Boeuf3, Joe Burns3,4, Laura Evgin3,4, Naomi De Silva3,4, Sara Cvancic3,4, Terri Robertson1, Ji-Eun Je7, Yeon-Sook Lee7, Kelley Parato3, Jean-Simon Diallo3, Aaron Fenster9, Manijeh Daneshmand3,4, John C. Bell3,4* & David H. Kirn1* 

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 tumor 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. 

*These authors contributed equally to this work.

Jenny-Kate Barkin