Pancreatic cancer
Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model
C Maletzki1, M Linnebacher2, B Kreikemeyer3, J Emmrich1
+ Author Affiliations

1Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Rostock, Germany
2Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Rostock, Germany
3Department of Medical Microbiology and Hospital Hygiene, Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany
C Maletzki, Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18055 Rostock, Germany; Claudia.Maletzki@uni-rostock.de
Revised 28 September 2007
Accepted 6 November 2007
Published Online First 19 November 2007
Abstract
Background: This study addressed the potential of bacteriolytic therapy using Streptococcus pyogenes in a syngeneic pancreatic carcinoma mouse model.

Methods: Panc02 tumours were either infected with S pyogenes or were treated with the equivalent volume of vehicle. In addition to assessment of tumour histology and immunohistochemistry, isolated splenocytes were analysed by flow cytometry. Interferon (IFN) γ secretion as a reaction of splenocytes against tumour cells was shown through the ELISpot technique. A cytotoxic effect of lymphocytes against tumour targets was detected by lactate dehydrogenase (LDH) release. Cytokine levels in serum were measured.

Results: A single application of live bacteria into established Panc02 tumours resulted in complete tumour regression. This antitumoural effect was accompanied by massive leucocyte infiltration into the tumours as well as a significant and sustained elevation of systemic levels of the proinflammatory cytokines IFNγ, tumour necrosis factor α and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFNγ-ELISpot, and most importantly in cellular cytotoxicity assays, indicating a tumour-specific immune response.

Conclusions: We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.

http://gut.bmj.com/content/57/4/483.abstract