Efficacy of tumor-targeting <i>Salmonella typhimurium</i> A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models

Abstract

// Yukihiko Hiroshima 1,2,3 , Yong Zhang 1 , Takashi Murakami 3 , Ali Maawy 2 , Shinji Miwa 1,2 , Mako Yamamoto 1,2 , Shuya Yano 1,2 , Sho Sato 3 , Masashi Momiyama 3 , Ryutaro Mori 3 , Ryusei Matsuyama 3 , Takashi Chishima 3 , Kuniya Tanaka 3 , Yasushi Ichikawa 3 , Michael Bouvet 2 , Itaru Endo 3 , Ming Zhao 1 and Robert M. Hoffman 1,2 1 AntiCancer, Inc., San Diego, CA, USA 2 Department of Surgery, University of California San Diego, San Diego, CA, USA 3 Yokohama City University Graduate School of Medicine, Yokohama, Japan Correspondence: Robert M. Hoffman or Ming Zhao, email: // Keywords : Pancreatic cancer, Salmonella typhimurium A1-R, patient-derived orthotopic xenograft (PDOX), orthotopic, nude mice, GFP, VEGF, anti-angiogenic therapy, bevacizumab, gemcitabine Received : September 17, 2014 Accepted : October 28, 2014 Published : October 28, 2014 Abstract The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.