Targeted deprivation of methionine with engineered Salmonella leads to oncolysis and suppression of metastasis in broad types of animal tumor models

Abstract

The strong dependency of almost all malignant tumors on methionine potentially offers a pathway for cancer treatment. We engineer an attenuated strain of Salmonella typhimurium to overexpress an L-methioninase with the aim of specifically depriving tumor tissues of methionine. The engineered microbes target solid tumors and induce a sharp regression in several very divergent animal models of human carcinomas, cause a significant decrease in tumor cell invasion, and essentially eliminate the growth and metastasis of these tumors. RNA sequencing analyses reveal that the engineered Salmonella reduce the expression of a series of genes promoting cell growth, cell migration, and invasion. These findings point to a potential treatment modality for many metastatic solid tumors, which warrants further tests in clinical trials.

Keywords: SGN1; engineered Salmonella; metastasis; methioninase; methionine dependency; oncolysis.