Novel insights into the role of Clostridium novyi-NT related combination bacteriolytic therapy in solid tumors

Abstract

Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure of conventional anticancer therapies. The areas of poor vascularization are insensitive to radiotherapy and chemotherapeutic drugs. Conversely, the hypoxic regions of tumors provide an ideal environment for anaerobic bacteria. The attenuated anaerobic bacterium, Clostridium novyi-NT (C. novyi-NT), is highly sensitive to oxygen and can target the destruction of hypoxic and necrotic areas of tumors, inducing oncolysis and characteristics indicative of an immune response. Theoretically, chemotherapy, radiotherapy and immunotherapy combined with bacterial therapy can be used as a novel means of treating solid tumors, promoting tumor regression and inhibiting metastasis formation with a notable beneficial effect. The present review discusses the molecular mechanisms of combined bacteriolytic therapy, predominantly focusing on C. novyi-NT, and summarizes the findings of previous studies on experimental animal models, including its efficacy and safety via different drug delivery routes. This strategy has great potential to overcome the limitations of conventional cancer therapy, resulting in improved treatments, and thus potentially improved outcomes for patients.

Keywords: C. novyi-NT; combination bacteriolytic therapy; intratumoral injection; intravenously injected; solid tumor regression.

Figure 1.

Comparison of intratumoral injection and intravenous management. (A) Direct intratumoral injection may allow relatively small doses of spores to be used, ensuring that a larger effective dose reaches the target tumor and is distributed around the tip of the needle. (B) Systemic injection requires large doses of injected spores; however, the proportion of spores delivered to the tumor is small (lower effective dose). Only the route of systemic administration can be selected for the treatment of disseminated cancers. C. novyi-NT, Clostridium novyi-NT.