The ideal bacteria should be able to evade the immune system upon entry to the body, and efficiently get to the tumor. Some trials had to be terminated due to severe toxicity.' Jaeseung Hahn, a postdoctoral research scientist in Danino and Leong's labs who co-led the project, noted, 'In clinical trials, these toxicities have been shown to be the critical problem, limiting the amount we can dose bacteria and compromising efficacy. They are also detected by the body's immune systems as foreign and dangerous, causing high inflammatory response - too much bacteria means high toxicity due to over-inflammation - or rapid bacteria elimination - too little bacteria means no therapeutic efficacy. Unlike many traditional drugs, these bacteria are alive and can proliferate within the body. While using bacteria for therapy is a new, alternative approach to treating a broad array of cancers, there are a number of challenges, in particular, their toxicity. Because iCAP alters bacterial interactions with immune systems (such as blood clearance and phagocytosis) in a directed manner, the team found that they could control the time to which bacteria can survive in human blood, by tuning how much IPTG they give to the iCAP E. They control the iCAP system by giving it an external cue - a small molecule called IPTG - that allows for programmable and dynamic alteration of the E. To do this, the researchers engineered a new CAP system, which they call inducible CAP, or iCAP. So we decided to try to build an effective on/off switch.' 'With CAP, these bacteria can temporarily evade immune attack without CAP, they lose their encapsulation protection and can be cleared out in the body.

coli strain Nissle 1917,' said Tetsuhiro Harimoto, a PhD student in Danino's lab who is the study's co-lead author. 'We hijacked the CAP system of a probiotic E. In nature, CAP helps many bacteria to protect themselves from attacks including immune systems. We also showed our system opens up a new bacteria delivery strategy in which we can inject bacteria to one accessible tumor, and have them controllably migrate to distal tumors such as metastases, cancer cells that spread to other parts of the body.'įor the study published today by Nature Biotechnology, the researchers focused on capsular polysaccharides (CAP), sugar polymers that coat bacterial surfaces. 'We can regulate the time that bacteria survive in human blood, and increase the maximum tolerable dose of bacteria. Sheng Professor of Biomedical Engineering. 'What's really exciting about this work is that we are able to dynamically control the system,' said Tal Danino, associate professor of biomedical engineering, who co-led the study in collaboration with Kam Leong, Samuel H.

Ivisible coat