Abstract 1230: Efficacy of Salmonella typhimurium A1-R and anti-VEGF therapy on a patient-derived orthotopic xenograft (PDOX) pancreatic cancer model

Abstract

Abstract We have previously developed the genetically-modified Salmonella typhimurium A1-R (A1-R) strain that selectively targets tumors and demonstrated that A1-R was able to eradicate primary and metastatic tumors in monotherapy in nude mouse models of various cancers including pancreatic cancer. The aim of this study was to examine the efficacy of A1-R treatment on VEGF-positive human pancreatic cancer in a patient derived orthotopic xenograft (PDOX) model in combination with anti-VEGF therapy. A VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) and VEGF-positive pancreatic cancer PDOX were orthotopically implanted in nude mice. The nude mice were treated in the following groups: (1) gemcitabine (GEM) (80 mg/kg, ip, weekly, 4 weeks); (2) GEM (80 mg/kg, ip, weekly, 4 weeks) + Bevacizumab (Bev) (5 mg/kg, ip, twice a week, 4 weeks); (3) GEM (80 mg/kg, ip, weekly, 2 weeks) + Bev (5 mg/kg, ip, twice a week, 2 weeks) → A1-R (1.5x108 CFU/body, ip, weekly, 2 weeks); and (4) saline (vehicle/control, ip, weekly, 4 weeks). The mean tumor weight of each group in the MiaPaCa-2-GFP model was as follows: (1) GEM; 775.9 ± 273.8 mg; (2) GEM/Bev; 413.5 ± 108.3 mg; (3) GEM/Bev→A1-R; 257.5 ± 57.1 mg; and (4) Control; 2655.4 ± 583.9 mg. GEM/Bev→A1-R significantly reduced tumor weight compared to GEM/Bev treatment in the MiaPaCa-2-GFP model (p=0.022). The tumor weight of each group in the PDOX model was as follows: (1) GEM; 263.1 ± 129.1 mg, (2) GEM/Bev; 65.9 ± 41.9 mg, (3) GEM/Bev→A1-R; 21.9 ± 6.2 mg and (4) Control; 998.8 ± 377.7 mg. GEM/Bev→A1-R significantly reduced tumor weight compared to GEM/Bev treatment in the PDOX model (p=0.029). These results demonstrate that A1-R is effective on pancreatic cancer in combination with anti-VEGF, including the PDOX model indicating the clinical potential of this combination. Citation Format: Yukihiko Hiroshima, Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Efficacy of Salmonella typhimurium A1-R and anti-VEGF therapy on a patient-derived orthotopic xenograft (PDOX) pancreatic cancer model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1230. doi:10.1158/1538-7445.AM2014-1230