New and Improved Cancer Immunotherapy
Immunotherapy focuses on boosting the immune system by providing it with more effective methods to fight off disease. It has thus become an invaluable tool in the fight against cancer. The main types of immunotherapy include synthetic monoclonal antibodies, cancer vaccines, and immune checkpoint inhibitors.
While the technique is promising, its results are not always successful as seen in the failure of a treatment administered one year ago which resulted in several patients’ deaths. Juno Therapeutics, the company responsible for running the experiment, presented the results of their internal investigation last week.
The treatment, known as chimeric antigen receptor (CAR)-T cell therapy, tested whether a new surface protein could help patients’ own immune cells kill cancer cells. However, scientists failed to account for differences in individual immune systems.
Their oversight had devastating consequences. Patient autopsies revealed a complete breakdown of the blood brain barrier, which likely led to severe neurotoxicity and edema.
According to Dr. Martin Fussenegger, “if you reprogram immune cells to kill cancer by fiddling around with your endogenous immune system, [there could be] some side effects.”
Thankfully, scientists have developed a new therapeutic which uses nonimmune mesenchymal stem cells (MSCs), minimizing the risk associated with reprogrammed immune cells.
The MSC signaling pathway activates when sensors on a cell’s surface interact with cancer cell antigens. This induces the release of an enzyme that converts 5-fluorocytosine (5-FC) to a toxic compound which kills cancer cells nearby.
Unlike CAR-T cell therapy, this technique is localized and controlled. Dr. Fusseneggar likens it to “an explosion, which could eventually kill the synthetic T cell, along with a couple of other cells around, mostly cancer cells.”
The experiment has only been performed in vitro but will be tested in rodent models. While the treatment is designed to combat breast cancer, its components are flexible enough to target many diseases of the immune system.