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Reprogramming of immune cells shown to fight off melanoma

1 November 2022

A new way of reprogramming our immune cells to shrink or kill off cancer cells has been shown to work in the otherwise hard to treat and devastating skin cancer, melanoma. The University of Bristol-led discovery, published in Advanced Science today [31 October], demonstrates a new way to clear early stage pre-cancerous and even late-stage tumour cells.

Using miniature artificial capsules called protocells designed to deploy reprogramming cargoes that are taken up by inflammatory cells (white blood cells), the scientists show they were able to transform these cells into a state that makes them more effective at slowing down the growth and killing of melanoma cells. They showed that this was possible for both animal and human immune cells.
 
The study is the first to test the capacity of a protocell to deliver cargoes for reprogramming immune cells and offers a promising novel target for the development of cancer immunotherapies.
 
Paul Martin, Bristol Cancer Network Co-Director and Professor of Cell Biology in the School of Biochemistry at the University of Bristol and one of the study's lead authors explained what happens when our immune system comes into contact with cancer cells: "Our immune cells have a surveillance capacity which enables them to detect pre-cancerous cells arising at any tissue site in the body. However, when immune cells encounter cancer cells they are often subverted by the cancer cells and instead tend to nourish them and encourage cancer progression. We wanted to test whether it might be possible to reprogramme our immune system to kill these cells rather than nurture them."
 

First, the team tested the proof of concept in zebrafish larvae which are used due to their translucency, allowing researchers to watch inflammatory immune cells interact with cancer cells in ways not possible in our own tissues.

Protocells loaded with anti-miR223 molecules that bind to and interfere with signalling machinery in the inflammatory immune cells and work by effectively prolonging their pro-inflammatory state, were shown to drive altered immune cell-cancer cell interactions, slowing the growth of cancerous cells and driving increased tumour cell death in the larvae.

 
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