Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model.
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) gamma 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 antitumoral 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 IFN gamma, tumour necrosis factor alpha and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFN gamma-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.
Maletzki
C
C
Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18055 Rostock, Germany. Claudia.Maletzki@uni-rostock.de
Linnebacher
M
M
Kreikemeyer
B
B
Emmrich
J
J
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D019496:Cancer Vaccines; D016207:Cytokines