MINI REVIEW article
Front. Microbiol.
Sec. Microbiotechnology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1603671
This article is part of the Research TopicMetabolic Engineering and Synthetic Biology for Sustainable Microbial Cell FactoriesView all 4 articles
Unlocking the Potential of Engineered Microbes in Immunotoxin-Based Cancer Therapy
Provisionally accepted
Quan Wang1,2
Rui Cao3Yuxing Xie1Zhuoyi Zhang1Xianguo Li1Yan Zhang4Haolin Luo2Hui Yao1Ping Xue1*Shuai Ni5- 1School of Pharmacy Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, P. R. China., Xianning, China
- 2Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
- 3Department of Anesthesiology, People’s Hospital of Xinzhou, Wuhan, China
- 4Department of Anesthesiology, Yunxi People's hospital, Shiyan, China
- 5Department of Neurosurgery, Union Hospital, Huazhong University of Science and Technology., Wuhan, China
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Immunotoxins (ITs), as targeted cancer therapies, confront limitations including off-target effects, immunogenicity, and inadequate tumor penetration, hindering clinical translation. Advances in tumor microenvironment (TME) understanding and genetic engineering have enabled engineered microorganisms such as attenuated Salmonella, E. coli Nissle 1917, and modified eukaryotic platforms (e.g., yeast, microalgae) to colonize tumors and act as efficient hosts for IT production. By integrating ITs into these microbes and employing precise circuits (e.g., phage lysis systems, signal peptide fusions), controlled secretion of recombinant immunotoxins (RITs) can be achieved. Balanced-lethal systems further enhance plasmid stability for sustained therapeutic delivery. This review highlights strategies leveraging engineered microbes to amplify IT efficacy, exemplified by preclinical successes like Salmonelladelivered TGFα-PE38 and E. coli-expressed anti-PD-L1-PE38. However, challenges persist, including dynamic TME interactions, systemic infection risks, manufacturing complexities and regulatory uncertainties demand resolution. By synergizing microbial targeting with RIT, this approach offers transformative potential for cancer therapy, yet requires multidisciplinary innovation to address technical, safety, and regulatory barriers for clinical adoption.
Keywords: immunotoxin, cancer therapy, Engineered microbes, circuits, tumor penetration
Received: 31 Mar 2025; Accepted: 23 May 2025.
Copyright: © 2025 Wang, Cao, Xie, Zhang, Li, Zhang, Luo, Yao, Xue and Ni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ping Xue, School of Pharmacy Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, P. R. China., Xianning, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.