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

Biomed Res Int. 2019 Apr 28:2019:1395138. doi: 10.1155/2019/1395138. eCollection 2019.

Abstract

Background: Anaerobic Clostridial spores (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 × 108 CFU/kg) or high dosage (3 × 108 CFU/kg) of Derivative Clostridial spore (DCG).

Results: Intravenous administration of the derivative of Clostridial 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 (<20/106 spleen 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/IFNγ secreting T cell response was induced when the tumour bearing mice received a low dose of DCG spore (1 × 108 CFU/kg), while a strong IFNγ response was elicited with a high dosage of DCG spore (3 × 108 CFU/kg).

Conclusion: The dosage of DCG spore will determine the types of the DCG induced immune responses.

MeSH terms

  • Animals
  • Clostridiales / genetics*
  • Clostridiales / immunology
  • Female
  • Human papillomavirus 16 / genetics
  • Humans
  • Interferon-gamma / genetics*
  • Interleukin-9 / genetics*
  • Mice
  • Oncogene Proteins, Viral / genetics
  • Repressor Proteins / genetics
  • Spores, Bacterial / genetics
  • Spores, Bacterial / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / microbiology
  • Transformation, Bacterial / genetics
  • Tumor Microenvironment / immunology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / microbiology
  • Uterine Cervical Neoplasms / virology

Substances

  • E6 protein, Human papillomavirus type 16
  • IFNG protein, mouse
  • Interleukin-9
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Interferon-gamma

Supplementary concepts

  • Paeniclostridium ghonii