The reprogramming of immune cells has been shown to fight melanoma

A new way to reprogram our immune cells to shrink or kill cancer cells has been shown to be effective
against melanoma, a devastating skin cancer that is difficult to treat.
The findings, led by the University of Bristol, were published Oct.
31 in the journal Advanced Science and demonstrate a new way to
remove early-stage precancerous and even advanced tumour cells.

Using tiny artificial capsules called "protocells," the scientists transferred "reprogrammed cargo" taken up by inflammatory cells (white blood cells) onto these cells, demonstrating that they were able to transform these cells into a state that made them more effective
at slowing the growth and killing of melanoma cells.
They showed that this is possible
for both animal and human immune cells.

This study is the first to test the ability of primary cells to transport cargo of reprogrammed immune cells and provides a promising new target for the development of cancer immunotherapies
.

Paul Martin, Professor of Cell Biology at the University of Bristol's School of Biochemistry and one of the study's lead authors, explains what happens when our immune system comes into contact with cancer cells: "Our immune cells have a surveillance ability that allows them to detect precancerous cells
that appear in any tissue part of the body.
However, when immune cells encounter cancer cells, they are usually subverted by cancer cells and instead tend to nourish cancer cells and encourage cancer development
.
We wanted to test whether it was possible to reprogram our immune system to kill these cells instead of growing them
.
”

First, the team tested a proof of concept in zebrafish larvae, and thanks to their translucency, the researchers could observe the interaction between inflammatory immune cells and cancer cells, an effect that would not have occurred in
our own tissues.

Protocytes loaded with anti-mir223 molecules bind to and interfere with signaling mechanisms in inflammatory immune cells, and by effectively prolonging their pro-inflammatory state, they have been shown to alter immune cell-cancer cell interactions, slow the growth of cancer cells, and increase the death
of tumor cells in larvae.

To find out if this approach could be scaled up as a viable therapeutic strategy for shrinking larger, more mature, and growing cancers, the experiment was repeated in adult fish with caudal fin melanoma, showing that this approach significantly inhibited the growth
of melanoma cells.

To fully investigate the feasibility of using protocytes to deliver "reprogrammed" anti-MIR223 cargo in humans, the experiment again used primary human immune cells from Toyer's laboratory, also located in Bristol School of
Biochemistry, for in vitro trials.
The results of the experiment show that protocells are able to efficiently deliver and reprogram human immune cells to develop
towards a longer-lasting pro-inflammatory and potentially anti-cancer state.

Professor Stephen Mann of the Bristol School of Chemistry and the Max Planck Bristol Centre for Minimal Biology added: "Our findings highlight the therapeutic benefits of harnessing host immunity to eradicate cancer and demonstrate the feasibility
of using protocytes to transport cargoes of reprogrammed innate immune cells.
" While our experiments on zebrafish were early preclinical studies, our results suggest that the same can happen to human immune cells, at least in vitro, and can be similarly reprogrammed to inhibit cancer growth
.
”

The research was supported
by funding from the Rafael del Pino Foundation in Spain, the Bristol Cancer Bequest, the EU Marie Curie Scholarship funded by HORIZON 2020, BBSRC (BrisEngBio), Wellcome, the Elizabeth Blackwell Institute, the European Research Council (ERC) and Cancer Research UK (CRUK).

Journal Reference:

1. Paco Ló pez‐Cuevas, Can Xu, Charlotte E.
   Severn, Tiah C.
   L.
   Oates, Stephen J.
   Cross, Ashley M.
   Toye, Stephen Mann, Paul Martin.
   Macrophage Reprogramming with Anti‐miR223‐Loaded Artificial Protocells Enhances In Vivo Cancer Therapeutic Potential.
   Advanced Science, 2022; 2202717 DOI: 10.
   1002/advs.
   202202717