Synthetic bacteria delivers nanobodies to kill cancer.

Cancer immunotherapy, which uses the body’s immune defenses to fight cancer, has transformed cancer treatment over the past decade, however, only a handful of solid tumours have responded to treatment, and systemic therapy often results in significant side effects. Designing therapies which can induce an anti-tumor immune response within a tumour without triggering systemic toxicity has posed a significant challenge. Now, a study from researchers at Columbia Engineering develops synthetic bacteria which are programmed to target and kill cancer cells without systemic side effects. The team state the new technique may lead to cancer therapies which treat the disease more precisely, without the side effects of conventional drugs. The study is published in the journal Nature Medicine.

Previous studies show a host’s immune cells can sometimes recognize and destroy cancer cells without assistance, however tumours may hide from the immune system by taking advantage of a gene called CD47. Normally, CD47 makes a protein which attaches itself to the surface of red blood cells, to cloak it from immune cells. Unfortunately mutations in cancer cells can cause them to switch on the CD47 gene, meaning the immune system sees them as harmless, allowing them to grow into live-threatening tumours. The current study develops synthetic microbes which release nanobodies engineered to target CD47 on cancer cells to leave the immune system free to attack tumours in mice.

The current study engineers a strain of bacteria with the ability to grow and multiply in tumours, specifically targetting CD47 within those tumours to avoid any systemic side effects. Five million of the synthetic microbes were injected into mouse tumours. Results show when bacteria numbers reach a critical threshold, 90% of the non-pathogenic E. coli self-destruct, spilling out nanobodies. Data findings show the nanobodies attach to CD47 proteins on the cancer cells, robbing them of their camouflage, leaving them vulnerable to attack from the immune system.

Results show fragments of the dead bacteria leak out of the tumour attracting the attention of immune cells, which then attack the uncloaked cancer cells. Data findings show inside the inflamed tumour, surviving bacteria starts to multiply again, with the majority committing suicide once more, delivering another wave of nanobodies and fragments. The team state their engineered bacteria clears treated tumours and reduces the incidence of tumour metastasis in multiple models.

The team surmise they have engineered programmable bacteria which clears cancerous tumours in mouse models, and also treats distant tumors that were not injected. For the future, the researchers state they plan to carry further studies of their engineered immunotherapeutic bacteria in a range of advanced solid tumour settings in mouse models.

Source: Columbia Engineering


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