What if doctors could use a delivery system that acts in the manner of a Trojan Horse, which can travel directly into cancer cells, release cancer-killing drugs, and thereby treat currently untreatable cancers? In fact, there is widespread media coverage of just such a delivery system based on non-toxic salmonella bacteria and developed in the lab of Neil S Forbes, a professor in the Chemical Engineering (ChE) Department and Institute for Applied Life Science.
The system can specifically target cancer cells, where it then releases its therapeutic drug payload with no negative side-effects. This groundbreaking research, based on what Forbes has called “super-safe salmonella bacteria,” was published recently in Nature Communications.
For the past 20 years, Forbes has been working on this delivery system based on non-pathogenic salmonella bacteria, which can use their own self-propulsion system to venture deep into tumors and deliver cancer-destroying agents, all without causing the vicious side effects of many chemotherapy treatments.
The present-day work, carried out by a dozen multidisciplinary researchers from UMass Amherst and elsewhere, could lead to effective, targeted therapies for currently untreatable cancers such as liver or metastatic breast cancer. As an example, some 840,000 people worldwide each year suffer from liver cancer, and there are currently few drugs available to treat the disease.
The delivery system was developed by Nele Van Dessel, a bioengineer and co-first author on the Nature Communications paper, as a post-doc in the Forbes lab. It uses a highly modified type of salmonella that is injected into the bloodstream. The protein used was developed with Professor Jeanne Hardy of the Chemistry Department, and the research was led by Van Dessel and Vishnu Raman of the ChE department and co-first author on the paper.
According to the News Office release, “The inability to penetrate solid tumor cell membranes has, until now, prevented researchers from being able to effectively target critical cancer pathways. Current delivery methods, such as nanoparticles, cell-penetrating peptides, and antibody drug conjugates, have limited efficacy because of their poor ability to enter cells, their inability to specifically target cancer cells, and their susceptibility to degradation from the cell’s natural protection against foreign invaders.”
The News Office release explains that this innovative work has demonstrated in the lab that not only can the salmonella system easily enter cells, but it can specifically target cancer cells to deliver drug proteins directly while leaving healthy cells alone. Once the protein payload is delivered, the bacteria dissipate and clear without causing harm.
“We can actually detect [the protein] in the tumors, but we can’t detect it in the livers and spleens” of mouse models, as Forbes told the News Office. “It delivers it just to the tumors.”
As Forbes explains, the trick is that salmonella travel directly and exclusively to cancer tumors.
“It sounds like science fiction, doesn’t it?” said Forbes in 2014. “But salmonella bacteria, in effect, are each little robots that can swim wherever they want. They have propellers in the form of flagella, they have sensors so they can tell where they’re going, and they’re also little chemical factories. So what we’re doing as engineers is controlling where they go, what chemical we want them to make, and when they make it.”
The evolution of that research has now reached the advanced stage reported in the Nature Communications paper.
For instance, as Forbes says, “With liver cancer, we’re seeing pre-clinical evidence that it has an anti-tumor effect. This is early, in just a few mice, but we’re keeping those tumors at bay using this therapy.”
As the Nature Communications paper concludes, “This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors.” (December 2021)