Clostridial Spores for Cancer Therapy: Targeting Solid Tumour Microenvironment

Table 1

Summary of current methods being researched in Clostridium-based cancer therapies.

Method	Premise	Target/drugs	Clostridium species being used	Reference
Clostridium directed enzyme prodrug therapy (CDEPT)	Clostridium is genetically engineered to express an enzyme which cleaves a prodrug into its cytotoxic form.	CD/F-FU	C. sporogenes; C. beijerinckii; C. acetobutylicum	[39]; [49]; [41]
		NTR/CB1954	C. beijerinckii; C. sporogenes	[37]; [40]
		NTR/PR-104
Administration of cytokines/cytotoxic agents	Clostridium is used to deliver agents (cytokines) to either act directly cytotoxic to cells or enhance immune system response to tumour cells.	murine TNFα	C. acetobutylicum	[41, 50, 51]
		IL-2	C. acetobutylicum	[42]
Clostridium directed antibody therapy (CDAT)	Clostridium is modified to produce highly specific antibodies against tumour antigens.	VHH against HIFα	C. novyi-NT	[45]
Combined bacteriolytic therapy (COBALT)	Clostridium which demonstrate direct antitumour effects are administered in conjunction with other known cancer therapies to increase oncolysis.	Clostridium/ mitomycin C and cytotaxin Clostridium/vinorelbine or docetaxel	C. novyi-NT; C. novyi-NT	[47]; [52]
Release of liposomal encapsulated drugs	Species of Clostridium which secrete lipid-degrading enzymes are used for the targeted release of liposome-encapsulated drugs at the tumour site.	Clostridium/Doxil	C. novyi-NT	[48]