L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

鼠伤寒沙门氏菌提供的 L-天冬酰胺酶可抑制实体肿瘤

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作者:Kwangsoo Kim, Jae Ho Jeong, Daejin Lim, Yeongjin Hong, Hyung-Ju Lim, Geun-Joong Kim, So-Ra Shin, Je-Jung Lee, Misun Yun, Robert A Harris, Jung-Joon Min, Hyon E Choy

Abstract

Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase), which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue.

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