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New method of reprogramming immune cells that works in melanoma
A new method of reprogramming our immune cells to shrink or kill cancer cells has proven effective in the otherwise difficult-to-treat and devastating skin cancer melanoma. The University of Bristol-led discovery, published today in Advanced Science [October 31], demonstrates a new way to eliminate early-stage precancerous lesions and even late-stage tumor cells. Using miniature artificial capsules called protocells that are designed to deploy reprogramming charges taken up by inflammatory cells (white blood cells), the scientists show that they were able to shift these cells into a state that makes them more effective at promoting growth and...
![Eine neue Methode zur Umprogrammierung unserer Immunzellen zum Schrumpfen oder Abtöten von Krebszellen hat sich bei dem ansonsten schwer zu behandelnden und verheerenden Hautkrebs Melanom als wirksam erwiesen. Die von der University of Bristol geleitete Entdeckung, die heute in Advanced Science veröffentlicht wurde [31 October]demonstriert einen neuen Weg, Krebsvorstufen im Frühstadium und sogar Tumorzellen im Spätstadium zu beseitigen. Unter Verwendung von künstlichen Miniaturkapseln, sogenannten Protozellen, die dazu bestimmt sind, reprogrammierende Ladungen einzusetzen, die von Entzündungszellen (weißen Blutkörperchen) aufgenommen werden, zeigen die Wissenschaftler, dass sie diese Zellen in einen Zustand versetzen konnten, der sie effektiver macht, um das Wachstum und das …](https://institut-der-gesundheit.com/cache/images/UQ-Forscher-erhalten-internationale-Mittel-zur-Bekaempfung-von-Melanomen-in-US-Truppen-1100.webp)
New method of reprogramming immune cells that works in melanoma
A new method of reprogramming our immune cells to shrink or kill cancer cells has proven effective in the otherwise difficult-to-treat and devastating skin cancer melanoma. The University of Bristol-led discovery, published today in Advanced Science [October 31], demonstrates a new way to eliminate early-stage precancerous lesions and even late-stage tumor cells.
Using miniature artificial capsules called protocells designed to deploy reprogramming charges taken up by inflammatory cells (white blood cells), the scientists show that they were able to shift these cells into a state that makes 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.
The study is the first to test a protocell's ability to deliver cargo for immune cell reprogramming and offers 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, explained what happens when our immune system comes into contact with cancer cells: "Our immune cells have a surveillance capacity that allows them to detect pre-cancerous cells that arise from any tissue location in the body. However, when immune cells encounter cancer cells, they often become infiltrated by the cancer cells and instead tend to feed them and promote cancer progression. We wanted to test whether it was possible to reprogram our immune system to kill these cells instead of nurturing them.”
First, the team tested proof of concept on zebrafish larvae, which are used because of their translucency, allowing researchers to observe how 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 disrupt the signaling machinery in the inflammatory immune cells, effectively prolonging their pro-inflammatory state, have been shown to drive altered interactions between immune cells and cancer cells, slowing the growth of cancer cells and driving increased tumor cell death in the larvae.
To determine whether this approach could be scaled up as a viable therapeutic strategy for shrinking larger, more established, and growing cancers, the experiment was repeated on adult fish with caudal fin melanomas, which showed that this approach significantly inhibited the growth of melanoma cells.
To fully explore the feasibility of using protocells to deliver “reprogrammed” anti-miR223 cargoes in humans, the experiment was re-performed using an in vitro assay using primary human immune cells from the Toye laboratory, also at the Bristol School of Biochemistry. The results of this experiment showed that the protocells were able to effectively direct and reprogram human immune cells into a more persistent pro-inflammatory and potentially anti-cancer state.
Professor Stephen Mann, from Bristol's School of Chemistry and the Max Planck Bristol Center for Minimal Biology, added: "Our results highlight the therapeutic benefits of harnessing host immunity to eradicate cancer and demonstrate the feasibility of using protocells to deliver cargoes for reprogramming innate immune cells. Our experiments in zebrafish are early ones preclinical studies, our results show that the same is possible for human immune cells, at least in vitro, and can be similarly reprogrammed to suppress cancer growth.”
The study was supported by grants from Spain's Rafael del Pino Foundation, a Bristol Cancer Bequest, an EU Marie Curie grant funded by HORIZON 2020, BBSRC (BrisEngBio), Wellcome, Elizabeth Blackwell Institute, the European Research Council (ERC) and Cancer Research UK (CRUK).
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Reference:
López-Cuevas, P., et al. (2022) Macrophage reprogramming with anti-miR223-loaded artificial protocells increases the therapeutic potential of in vivo cancer. Advanced science. doi.org/10.1002/advs.202202717.
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