Bacteria can be engineered to multiply selectively inside tumors, thus inhibiting tumor growth. The bacteria could also be programmed to deliver drugs and proteins directly to the tumors to kill them; there are, however, challenges to overcome before bacterial therapy for cancer could be a viable treatment.
One of the main problems is the immune system, which recognizes the bacteria and attacks them. In clinical trials, the immune response has caused problems, as the bacteria have been detected by the immune system and determined to be dangerous, triggering a dangerous inflammatory response. In some studies, trials had to be terminated due to severe toxicity. The immune response means the dose of bacteria that can be tolerated is relatively low, which reduces the efficacy of any treatment.
Researchers at Columbia Engineering have been exploring ways to hide therapeutic bacteria from the immune system to allow higher doses of the bacteria to be used. “In this study, we developed a genetically encoded microbial encapsulation system with a tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery,” explained the researchers.
The researchers used sugar polymers on the surface of bacteria – capsular polysaccharides (CAP) – to temporarily hide the bacteria from the immune system. In this case, the researchers used the CAP system of the probiotic E. coli strain Nissle 1917. With CAP, the bacteria evade the immune system and without it, they lose their capsular protection and are cleared from the body by the immune system. The length of time the bacteria can hide depends on how much isopropyl-b-D-thiogalactopyranoside (IPTG) is given to the bacteria. Since the duration they can evade the immune system can be controlled, the researchers have basically created an on-off switch. This new system is called inducible CAP (iCAP).
Using this new system, the researchers demonstrated they could control the time that the bacteria could survive in human blood and were also able to increase the tolerable dose of bacteria by a factor of 10. The researchers also demonstrated it was possible to inject bacteria into an accessible tumor and control their migration to distal tumors, such as metastases.
“Bacterial cancer therapy holds unique advantages over conventional drug therapy, such as efficient targeting of the tumor tissue and programmable drug release. Potential toxicity has been limiting its full potential. The cloaking approach presented in this study may address this critical issue,” said lead researcher Jaeseung Hahn, Ph.D.
You can read more about the study in the paper – A programmable encapsulation system improves delivery of therapeutic bacteria in mice– which was recently published in Nature Biotechnology. DOI: 10.1038/s41587-022-01244-y