E Antonio Chiocca, John S Yu, Rimas V Lukas, Isaac H Solomon, Keith L Ligon, Hiroshi Nakashima, Daniel A Triggs, David A Reardon, Patrick Wen, Brittany M Stopa, Ajay Naik, Jeremy Rudnick, Jethro L Hu, Priya Kumthekar, Bakhtiar Yamini, Jill Y Buck, Nathan Demars, John A Barrett, Arnold B Gelb, John Zhou, Francois Lebel, Laurence J N Cooper
Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application is limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated by an oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection of recurrent high-grade glioma. Resection cavity walls were injected (day 0) with a fixed dose of the hIL-12 vector (Ad-RTS-hIL-12). The oral activator for hIL-12, veledimex (VDX), was administered preoperatively (assaying blood-brain barrier penetration) and postoperatively (measuring hIL-12 transcriptional regulation)...
August 14, 2019: Science Translational Medicine