title: 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.
authors: Jennerex Inc., 450 Sansome Street, 16th floor, San Francisco, California 94111, USA.
authors: Caroline J
authors: CJ
authors: Breitbach
authors: James
authors: J
authors: Burke
authors: Derek
authors: D
authors: Jonker
authors: Joe
authors: J
authors: Stephenson
authors: Andrew R
authors: AR
authors: Haas
authors: Laura Q M
authors: LQ
authors: Chow
authors: Jorge
authors: J
authors: Nieva
authors: Tae-Ho
authors: TH
authors: Hwang
authors: Anne
authors: A
authors: Moon
authors: Richard
authors: R
authors: Patt
authors: Adina
authors: A
authors: Pelusio
authors: Fabrice
authors: F
authors: Le Boeuf
authors: Joe
authors: J
authors: Burns
authors: Laura
authors: L
authors: Evgin
authors: Naomi
authors: N
authors: De Silva
authors: Sara
authors: S
authors: Cvancic
authors: Terri
authors: T
authors: Robertson
authors: Ji-Eun
authors: JE
authors: Je
authors: Yeon-Sook
authors: YS
authors: Lee
authors: Kelley
authors: K
authors: Parato
authors: Jean-Simon
authors: JS
authors: Diallo
authors: Aaron
authors: A
authors: Fenster
authors: Manijeh
authors: M
authors: Daneshmand
authors: John C
authors: JC
authors: Bell
authors: David H
authors: DH
authors: Kirn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology*; D030781:Organisms, Genetically Modified / Q000502:physiology; D011212:Poxviridae / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D001616:beta-Galactosidase