Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 28, 2010; 16(28): 3546-3552
Published online Jul 28, 2010. doi: 10.3748/wjg.v16.i28.3546
Bacteriolytic therapy of experimental pancreatic carcinoma
Claudia Maletzki, Michael Gock, Ulrike Klier, Ernst Klar, Michael Linnebacher
Claudia Maletzki, Michael Gock, Ulrike Klier, Ernst Klar, Michael Linnebacher, Department of General, Vascular, Thoracic and Transplantation Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock, 18057 Rostock, Germany
Author contributions: Maletzki C, Gock M and Klier U performed the majority of experiments; Linnebacher M, Klar E and Gock M provided financial support for this work; Maletzki C, Gock M and Linnebacher M designed the study and wrote the manuscript; Maletzki C and Gock M contributed equally to this article.
Supported by Grant Number 2006/A29 from the Else-Kröner Fresenius Stiftung to Linnebacher M and Klar E
Correspondence to: Dr. Michael Linnebacher, Department of General, Vascular, Thoracic and Transplantation Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, Germany. michael.linnebacher@med.uni-rostock.de
Telephone: +49-381-4946048 Fax: +49-381-4946002
Received: January 15, 2010
Revised: February 4, 2010
Accepted: February 11, 2010
Published online: July 28, 2010
Abstract

AIM: To investigate the effectiveness of Clostridium novyi (C. novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic, immunocompetent Panc02/C57Bl/6 model.

METHODS: C. novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes. Systemic immune responses in peripheral blood and spleen were examined by flow cytometry. Supplementary, cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed.

RESULTS: Application of spores identified, that (1) small tumors (< 150 mm3) were completely unaffected (n = 10); (2) very large tumors (> 450 mm3) responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n = 6); and (3) an optimal treatment window exists for tumors of approximately 250 mm3 (n = 21). In this latter group, all tumor-bearing animals had complete tumor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed (tumor volume at day 28: 197.8 ± 87.3 mm3vs 500.1 ± 50.9 mm3, P < 0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system.

CONCLUSION: The observed complete tumor regression is encouraging and shows that immunotherapy with C. novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.

Keywords: Bacteriolytic immunotherapy, Clostridium novyi-NT, Immune response, Pancreatic carcinoma