Fatemeh Abedi Jafari
1 
, Asghar Abdoli
2* , Reza Pilehchian
3, Neda Soleimani
1, Seyed Masoud Hosseini
11 Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
2 Department of Hepatitis and HIV, Pasteur Institute of Iran (IPI), Tehran, Iran
3 Specialized Clostridia Research Laboratory, Department of Anaerobic Vaccine Research and Production, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization (AREEO), Karaj, Alborz, Iran
Abstract
Introduction: Hypoxia context is highly specific for tumors and represents a unique niche which is not found elsewhere in the body. Clostridium novyi is an obligate anaerobic bacterium. It has a potential to treat tumors. The aim of this study was to produce the C. novyi nontoxic spores and to investigate its oncolytic effect on breast cancer in mice model.
Methods: Primarily, the lethal toxin gene in C. novyi type B was removed. Colonies were isolated using PCR testing. To assure the removal of alpha-toxin, plasmid extraction and in vivo assay were conducted. Next, to treat breast cancer model in different sizes of tumors, a single dose of spores of C. novyi nontoxic was tested.
Results: The results denoted that C. novyi nontoxic lost lethal toxin and appeared to be safe. For smaller than 1000 mm3 tumors, a single dose of C. novyi nontoxic was able to cure 100% of mice bearing breast tumors. Hence the mice remained free of tumor relapse. Tumors larger than 1000 mm3 were not cured by a single dose of C. novyi nontoxic treatment.
Conclusion: The experiment concluded that the C. novyi nontoxic might be a suitable and safe candidate, a novel therapeutic approach to encounter such hypoxic regions in the center of tumors. Research also showed that bacteriolytic therapy by C. novyi nontoxic could lead to regression in small tumor.