THERAPY OF PANCREATIC CARCINOMA IN A MOUSE MODEL USING STREPTOCOCCUS PYOGENES

Abstract

Background & Aims: In the present study, we investigated the potential of intratumoral injection of Streptococcus pyogenes to achieve a bacteria related immune response against tumor cells followed by tumor regression. Material & Methods: In a syngeneic mouse model, s.c. 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, flow cytometry analysis of splenocytes was performed to detect lymphocyte subpopulations, as well as ELISPOT IFN-γ assays to characterize the immune response. Using LDH release we determined the cytotoxic effect of lymph node-derived lymphocytes against tumour cells. Additionally, cytokine levels in serum were measured. Results: A single intratumoral injection of S. pyogenes caused regression of pancreatic carcinoma in animals within 28 days. Histologic analyses revealed massive infiltration of leukocytes into tumour tissues. In line with this, the amount of IFN-γ secreting splenocytes was up to 3-fold higher at day 7 and at day 14 after infection, but progressively decreased up to day 28. Concomitantly, cytotoxic activity of lymph node-derived lymphocytes against tumour cells increased up to 80% at day 28 after S. pyogenes infection. Furthermore, serum levels of proinflammatory cytokines were significantly elevated in infected animals. Conclusions: The application of S. pyogenes leads to complete regression of Panc02 tumour in syngeneic animals, both through direct cell lysis and indirect by enhanced immune reaction. Taken together, the data suggest that application of S. pyogenes is a promising new therapeutic approach for tumour disease. Further studies will investigate strategies to control bacteria infection.