A99: The influence of live Streptococcus pyogenes on the growth of solid murine tumors

Abstract

Ability of Streptococcus pyogenes to fight cancer was discovered and clinically tested more than 100 years ago (Coley, 1897), but the mechanisms of these effects are unknown. Recently several murine models demonstrating the anti-cancer activity of Group A Streptococcus (GAS) M49 were established (Maletzki, 2008). The present study is devoted to investigation of anti-cancer activity of GAS M39 strains. Materials and Methods Tumor cells were injected subcutaneously in concentration of 200,000 cells per animal. Two solid tumor models were used: hepatoma 22a in C3HA mice and sarcoma 37 in Swiss mice. GAS (wild and mutant strains) were injected into the tumor 2 × 104 per animal twice with a 5-day-interval. The influence of GAS on tumor growth was evaluated by measurement of tumor diameter and animal survival. Inactivation of M protein (emm) gene was generated by insertional mutagenesis after cloning the fragment of the emm gene in suicidal plasmid pT7ermB.The plasmid was introduced into GAS by electroporation. Insertion had been proved by DNA sequencing. Results Intratumoral injections of wild GAS M39 strain did not influence on tumor size in mice bearing hepatoma 22a and sarcoma 37. The second injection of GAS enhanced inhibition of the tumor growth, but increased the death rates. The treatment by emm mutant strain caused the inhibition of tumor growth and showed less mortality rate both tumor models. The average number of completely cured animals was 10%. Conclusion Inactivation of emm gene in GAS M39 strain resulted in increased anti-tumor activity and decreased lethality rate. We hypothesized that the absence of anti-phagocytic M protein may increase phagocytosis of GAS by macrophages and thus enhance their antitumor activity.