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.