Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies

Vishnu Raman; Chinmay P Deshpande; Shradha Khanduja; Lars M Howell; Nele Van Dessel; Neil S Forbes

doi:10.1016/j.chom.2023.09.006

Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies

Cell Host Microbe. 2023 Oct 11;31(10):1574-1592. doi: 10.1016/j.chom.2023.09.006.

Authors

Vishnu Raman¹, Chinmay P Deshpande², Shradha Khanduja², Lars M Howell², Nele Van Dessel³, Neil S Forbes⁴

Affiliations

¹ Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA; Ernest Pharmaceuticals, LLC, Hadley, MA, USA.
² Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
³ Ernest Pharmaceuticals, LLC, Hadley, MA, USA.
⁴ Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA; Molecular and Cell Biology Program, University of Massachusetts, Amherst, Amherst, MA, USA; Institute for Applied Life Science, University of Massachusetts, Amherst, Amherst, MA, USA. Electronic address: forbes@umass.edu.

PMID: 37827116
DOI: 10.1016/j.chom.2023.09.006

Abstract

Many systemically administered cancer therapies exhibit dose-limiting toxicities that reduce their effectiveness. To increase efficacy, bacterial delivery platforms have been developed that improve safety and prolong treatment. Bacteria are a unique class of therapy that selectively colonizes most solid tumors. As delivery vehicles, bacteria have been genetically modified to express a range of therapies that match multiple cancer indications. In this review, we describe a modular "build-a-bug" method that focuses on five design characteristics: bacterial strain (chassis), therapeutic compound, delivery method, immune-modulating features, and genetic control circuits. We emphasize how fundamental research into gut microbe pathogenesis has created safe bacterial therapies, some of which have entered clinical trials. The genomes of gut microbes are fertile grounds for discovery of components to improve delivery and modulate host immune responses. Future work coupling these delivery vehicles with insights from gut microbes could lead to the next generation of microbial cancer therapy.

Keywords: Clostridium; E. coli; Listeria; Salmonella; Yersenia; bacterial cancer therapies; therapeutic design.

Publication types

Review

MeSH terms

Host Microbial Interactions*
Humans
Neoplasms* / therapy
Synthetic Biology / methods