• Clever approach
• From mice to people
What is already known on this topic
Cancer immunotherapy — a type of treatment that aims at boosting the body’s own immune system to fight off tumors — has grown explosively over the past decade. But only a handful of tumors respond to the treatment, and therapy often results in significant side effects.What this research adds
Researchers have engineered a strain of non-pathogenic Escherichia coli that can colonize solid tumors in mice and deliver immunotherapy drugs. The treatment resulted not only in a complete tumor regression in a mouse model of lymphoma, but also in a significant control of distant tumor lesions.Conclusions
The approach could be used to stimulate the immune system to seek out and clear difficult-to-treat tumors.
Researchers have engineered bacteria that can colonize tumors and deliver immunotherapy drugs. The study, done in mice, was published in the journal Nature Medicine.
Cancer immunotherapy — a type of treatment that aims at boosting the body’s own immune system to fight off tumors — has grown explosively over the past decade, but only a handful of tumors respond to the treatment, and therapy often results in significant side effects.
To find an approach that can induce an anti-tumor response without triggering toxicity, Sreyan Chowdhury at Columbia University and his colleagues set out to engineer bacteria as therapeutic systems to deliver drugs in solid tumors.
Clever approach
The approach relies on bacteria that grow to a certain level, lyse and release their contents, and then grow back again. Chowdhury and his team decided to use Escherichia coli bacteria, which grow outside of human cells, are non-pathogenic, and persist for at least 6 days after being injected into a tumor.
When the number of Escherichia coli reach a critical threshold within the tumor, the bacteria are programmed to self-destruct and release an antibody fragment called a nanobody.
Cancer cells often express on their surface a “don’t eat me” signal, which protects them from being destroyed by immune cells. So the researchers used a nanobody that targets the cells’ “don’t eat me” signal, resulting in a potent immune reaction against the tumor.
Because “don’t eat me” signals are present elsewhere in the body, and systemic targeting of these signals could result in toxicity, the team engineered Escherichia coli to target only the “don’t eat me” signals within the tumor.
From mice to people
Using this approach in a mouse model of lymphoma, the researchers were able to show robust tumor-specific immune responses that resulted not only in a complete tumor regression at the injection site, but also in a significant control of distant tumor lesions.
The team is now performing further analyses to test the safety of the engineered bacteria in a range of mouse models of solid tumors. If those tests succeed, the approach may lead to a clinical trial in people with cancer, the scientists say.
