Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice

Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5×107 CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v. treatment. Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration.

[1]  R. Hoffman,et al.  Comparison of the selective targeting efficacy of Salmonella typhimurium A1-R and VNP20009 on the Lewis lung carcinoma in nude mice , 2015, Oncotarget.

[2]  M. Bouvet,et al.  Efficacy of Tumor‐Targeting Salmonella Typhimurium A1‐R on Nude Mouse Models of Metastatic and Disseminated Human Ovarian Cancer , 2014, Journal of cellular biochemistry.

[3]  Robert S. Benjamin,et al.  Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses , 2014, Science Translational Medicine.

[4]  I. Endo,et al.  Efficacy of Salmonella typhimurium A1‐R Versus Chemotherapy on a Pancreatic Cancer Patient‐Derived Orthotopic Xenograft (PDOX) , 2014, Journal of cellular biochemistry.

[5]  Mine Yarim Meric Koksal Irem Durmaz,et al.  Synthesis and anticancer screening studies of benzhydrylpıperazıne derivatives , 2014 .

[6]  I. Endo,et al.  Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells , 2013, Cell cycle.

[7]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[8]  K. König,et al.  Cancer-cell killing by engineered Salmonella imaged by multiphoton tomography in live mice. , 2012, Anticancer research.

[9]  I. Endo,et al.  Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model , 2012, Cell cycle.

[10]  R. Hoffman The preclinical discovery of bacterial therapy for the treatment of metastatic cancer with unique advantages , 2012, Expert opinion on drug discovery.

[11]  Fang Liu,et al.  Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity , 2010, Cell cycle.

[12]  N. Forbes Engineering the perfect (bacterial) cancer therapy , 2010, Nature Reviews Cancer.

[13]  Katsuhiro Hayashi,et al.  Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium , 2010, Cell proliferation.

[14]  W. Falk,et al.  Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α , 2009, PloS one.

[15]  K. Yamauchi,et al.  Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice. , 2009, Anticancer research.

[16]  K. Yamauchi,et al.  Systemic targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma in nude mice with a tumor-selective strain of Salmonella typhymurium , 2009, Cell cycle.

[17]  M. Blagosklonny “Targeting the absence” and therapeutic engineering for cancer therapy , 2008, Cell cycle.

[18]  M. Blagosklonny Cancer stem cell and cancer stemloids: From biology to therapy , 2007, Cancer biology & therapy.

[19]  Meng Yang,et al.  Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer , 2007, Proceedings of the National Academy of Sciences.

[20]  Meng Yang,et al.  Targeted therapy with a Salmonella typhimurium leucine-arginine auxotroph cures orthotopic human breast tumors in nude mice. , 2006, Cancer research.

[21]  M. Blagosklonny Target for cancer therapy: proliferating cells or stem cells , 2006, Leukemia.

[22]  M. Blagosklonny Teratogens as Anticancer Drugs , 2005, Cell cycle.

[23]  Meng Yang,et al.  Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Blagosklonny Matching targets for selective cancer therapy. , 2003, Drug discovery today.

[25]  M. Blagosklonny Tissue-selective therapy of cancer , 2003, British Journal of Cancer.

[26]  R. Bast,et al.  Progress in the management of gynecologic cancer: consensus summary statement. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  K. Kinzler,et al.  Combination bacteriolytic therapy for the treatment of experimental tumors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Blagosklonny Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells , 2001, Leukemia.

[29]  Jun Amano,et al.  Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors , 2001, Breast Cancer Research and Treatment.

[30]  J. Trent,et al.  Comparative properties of five human ovarian adenocarcinoma cell lines. , 1985, Cancer research.

[31]  John Mao,et al.  Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.