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 tumors 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 tumor without triggering systemic toxicity has posed a significant challenge.

Now, a study from researchers at Columbia Engineering develops synthetic bacteria programmed to target and kill cancer cells without systemic side effects. The team states the new technique may lead to cancer therapies possessing the ability to treat the disease more precisely, without the side effects of conventional drugs. The study is published in the journal Nature Medicine.

An invisibility cloak for cancer

Previous studies show a host’s immune cells can sometimes recognize and destroy cancer cells without assistance, however, tumors may hide from the immune system by taking advantage of a gene called CD47. Normally, CD47 makes a protein to enable it to attach to the surface of red blood cells to cloak itself 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 life-threatening tumors. The current study develops synthetic microbes programmed to release nanobodies engineered to target CD47 on cancer cells to leave the immune system free to attack tumors in mice.

The current study engineers a strain of bacteria with the ability to grow and multiply in tumors, specifically targetting CD47 within those tumors to avoid any systemic side effects. Five million of the synthetic microbes were injected into mouse tumors.

Making cancer easy to kill

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 tumor attracting the attention of immune cells, which then attack the uncloaked cancer cells. Data findings show inside the inflamed tumor, surviving bacteria start to multiply again, with the majority committing suicide once more, delivering another wave of nanobodies and fragments. The team states their engineered bacteria clears treated tumors and reduces the incidence of tumor metastasis in multiple models.

The team surmises they have engineered programmable bacteria capable of clearing cancerous tumors in mouse models, as well as 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 tumor settings in mouse models.

Source: Columbia Engineering

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