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Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model
  1. C Maletzki1,
  2. M Linnebacher2,
  3. B Kreikemeyer3,
  4. J Emmrich1
  1. 1
    Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Rostock, Germany
  2. 2
    Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Rostock, Germany
  3. 3
    Department of Medical Microbiology and Hospital Hygiene, Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany
  1. C Maletzki, Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18055 Rostock, Germany; Claudia.Maletzki{at}uni-rostock.de

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.

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Footnotes

  • Competing interests: None declared.

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