The Dosage of the Derivative ofClostridium Ghonii(DCG) Spores Dictates Whether an IFNγ/IL-9 or a Strong IFNγResponse Is Elicited in TC-1 Tumour Bearing Mice

Abstract

Background. AnaerobicClostridialspores (CG) cause significant oncolysis in hypoxic tumour microenvironment and result in tumour regression in both animal models and clinical trials. The immune mediated response plays a critical role in the antitumour effect by the anaerobic spore treatment.Method. Human papillomavirus 16 E6/E7 transformed TC-1 tumour bearing mice were intravenously administered with low (1 × 108CFU/kg) or high dosage (3 × 108CFU/kg) of DerivativeClostridialspore (DCG).Results. Intravenous administration of the derivative ofClostridial ghonii(DCG) spores leads to both tumour and systemic inflammatory responses characterized by increased IFNγ/IL-9 secreting T cells in the spleen and the tumour. Low numbers of antigen specific T cells (<20/106spleen cells) in the spleen of the tumour bearing mice are also detected after intravenous DCG delivery. Interestingly, our results showed that a mixed IL-9/IFNγsecreting T cell response was induced when the tumour bearing mice received a low dose of DCG spore (1 × 108CFU/kg), while a strong IFNγresponse was elicited with a high dosage of DCG spore (3 × 108CFU/kg).Conclusion. The dosage of DCG spore will determine the types of the DCG induced immune responses.