Engineering Bacteria for Cancer Immunotherapy by Inhibiting IDO Activity and Reprogramming CD8+ T Cell Response

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2024 Dec 18

PMID 39693352

Authors

Heng Wang

Fang Xu

Chenlu Yao

Huaxing Dai

Jialu Xu

Bingbing Wu

Bo Tian

Xiaolin Shi

Chao Wang

Affiliations

Soon will be listed here.

Abstract

Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face significant challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing (L-Trp CB) strain that can colonize tumors strictly following systemic administration. We revealed that butyrate produced by L-Trp CB can inhibit IDO activity, preventing tryptophan catabolism and kynurenine accumulation in tumors. In addition, the large released tryptophan by L-Trp CB can provide discrete signals that support CD8+ T cell activation and energy metabolism within the tumor microenvironment. We observed that L-Trp CB significantly restored the proportion and function of CD8+ T cells, leading to significantly delayed tumor growth in both mouse and rabbit multiple tumor models with limited side effects. We here provide a synthetic biology treatment strategy for enhanced tumor immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response in tumors.

Citing Articles

Living Bacteria: A New Vehicle for Vaccine Delivery in Cancer Immunotherapy.

Yang M, Zhong P, Wei P Int J Mol Sci. 2025; 26(5).

PMID: 40076679 PMC: 11900161. DOI: 10.3390/ijms26052056.

Engineering bacteria for cancer immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response.

Wang H, Xu F, Yao C, Dai H, Xu J, Wu B Proc Natl Acad Sci U S A. 2024; 121(52):e2412070121.

PMID: 39693352 PMC: 11670085. DOI: 10.1073/pnas.2412070121.

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