Salmonella enterica Typhimurium engineered for nontoxic systemic colonization of autochthonous tumors. (16th March 2021)

• Record Type: Journal Article
• Authors: Augustin, Lance B.; Milbauer, Liming; Hastings, Sara E.; Leonard, Arnold S.; Saltzman, Daniel A.; Schottel, Janet L.
• Is Part Of: Journal of drug targeting. Volume 29:Number 3(2021)
• Page Start: 294
• Page End: 299
• Publication Date: 2021-03-16
• Subjects: Bacterial cancer therapy -- vascular disruption -- autochthonous tumour colonisation -- BALB-neuT -- virulence-attenuated Salmonella Typhimurium; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2020.1818759
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: Much of the bacterial anticancer therapy being developed relies on the ability of bacteria to specifically colonise tumours. Initial attempts to translate promising Salmonella enterica Typhimurium ( S . Typhimurium) preclinical results to the clinical setting failed, primarily due to lack of tumour colonisation and the significant toxicities from systemically administered Gram-negative bacteria. To address the difference in results between preclinical experiments performed in mice with transplant tumours and clinical trials in human volunteers with autochthonous tumours, a genetically engineered mouse model of breast cancer (BALB-neuT) was utilised to develop a strain of virulence-attenuated S . Typhimurium capable of robust colonisation of autochthonous tumours. Several genes that code for bacterial surface molecules, responsible for signalling a toxic immune response against the bacteria, were mutated. The resulting S. Typhimurium strain, BCT2, allowed non-toxic intravenous administration of 3 × 10 6 colony forming units of bacteria in tumour-burdened mice when combined with a vascular disruption agent to induce intratumoral necrotic space and facilitate bacterial colonisation.