Therapeutic bacteria can now ‘hide’ from being hunted down by immune systems, thanks to pioneering work performed at Columbia University in the US.
Researchers report that they have developed a ‘cloaking’ system that temporarily hides the beneficial bugs from immune systems, allowing them to more effectively deliver drugs to tumours and kill cancer cells in mice.
By manipulating the microbes’ DNA, scientists programmed gene circuits that control the bacteria’s surface, encapsulating it in a molecular cloak. First revealed in Nature Biotechnology, the innovation draws on capsular polysaccharides (CAP), sugar polymers that coat bacterial surfaces. CAP help bacteria protect themselves from attacks, including from immune systems.
Tetsuhiro Harimoto, a PhD student and the study’s co-lead author, explained that the researchers hijacked the CAP system of probiotic E. coli strain Nissle 1917.
“With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch,” added Harimoto.
The technique means the time that bacteria survive in human blood can now be regulated, permitting an increase in the maximum tolerable dose of bacteria in the body. It also offers to tantalising prospect of bacteria being injected to one accessible tumour and sent to distal tumors such as metastases which have spread to other parts of the body.
Yet, 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. Unlike many traditional drugs, these bacteria are alive and can proliferate within the body.
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.
Jaeseung Hahn, a postdoctoral research scientist 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. Some trials had to be terminated due to severe toxicity.”
