Melanoma, a deadly and difficult-to-treat skin cancer, has been proven to respond to a novel method of reprogramming our immune cells to shrink or kill off malignant cells. The cell reprogramming made by researchers at the University of Bristol, which was published in Advanced Science today [31 October], shows a new method for eliminating early-stage precancerous and even late-stage tumor cells.
The researchers demonstrate that they were able to reprogramme inflammatory cells (white blood cells) into a state that increases their efficiency at inhibiting the growth and eliminating melanoma cells by using tiny artificial capsules called protocells designed to deploy cell reprogramming cargoes that are taken up by inflammatory cells. They demonstrated that both human and animal immune cells were capable of doing this.
The research shows a promising new target for making cancer immunotherapies, and it is the first time that the ability of a protocell to carry payloads for changing immune cells has been looked at.
One of the study’s principal authors and professor of cell biology at the University of Bristol, Paul Martin, described what transpires when cancer cells are exposed to our immune system “Our immune cells have the ability to monitor any tissue site in the body for the emergence of pre-cancerous cells. However, when immune cells come into contact with cancer cells, the cancer cells frequently manipulate them and instead have a tendency to feed them, promoting the spread of the disease. We wanted to see if it was possible to rewire our immune system to target these cells for destruction rather than growth.
The proof of concept was first tested on zebrafish larvae because they are clear. This lets researchers see how inflammatory immune cells interact with cancer cells in ways that would be impossible in our own tissues.
It has been demonstrated that protocells loaded with anti-miR223 molecules alter interactions between immune cells and cancer cells, slowing the growth of cancerous cells and increasing tumor cell death in larvae. These molecules attach to inflammatory immune cells and mess with their signaling machinery. This keeps them in a pro-inflammatory state for longer.
The experiment was replicated in adult fish with tailfin melanomas to determine whether this approach might be scaled up as a practical treatment strategy for diminishing larger, more established, and developing tumors. The results showed that this approach effectively suppressed melanoma cell growth.
The experiment was repeated using an in vitro assay with primary human immune cells from the Toye lab, also at Bristol’s School of Biochemistry, to completely investigate the viability of utilizing protocells to deliver “reprogramming” anti-miR223 payloads in people. The results of the experiment showed that the protocells could successfully transfer and reprogram human immune cells to make them more pro-inflammatory and possibly anti-cancer.
Additionally, Professor Stephen Mann of the Max Planck Bristol Centre for Minimal Biology and the School of Chemistry at Bristol said: “Our findings demonstrate the viability of using protocells to deliver cargoes for cell reprogramming innate immune cells and highlight the therapeutic advantages of using host immunity to eliminate cancer. Even though our research on zebrafish is still preliminary pre-clinical research, our results suggest that human immune cells can also be reprogrammed to stop cancer cells from growing, at least in vitro.
The study was paid for by the European Research Council (ERC), the Wellcome Trust, the Elizabeth Blackwell Institute, the European Union’s Marie Curie Fellowship through Horizon 2020, the Rafael del Pino Foundation in Spain, and Cancer Research UK (CRUK).
