Scientists at the University of Washington and the UK Medical Research Council’s Molecular Biology Laboratory have designed a new protein substance that they say could improve the effectiveness of immunotherapies by affecting cell signaling.
The new flat material, created with two types of proteins as building blocks, could inhibit the sexual ability of cells to control signals, which could inhibit a natural process that limits impact. immunotherapies, as described in a study published in Nature.
The findings could inspire new therapies for infectious diseases and inflammatory disorders and could also inform the design of future multiprotein products to alter cell responses, the researchers said.
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Cell signals occur when cell protein receptors on its surface bind to molecules such as drugs, hormones and neurotransmitters. But to ensure that the response that triggered the signaling is immobilized, so it can function at a later time, cells typically cut off signals by circulating their activated receptor and molecule. stimulatory in a process called endocytosis.
“This tendency of cells to ingest receptors appears to reduce the efficacy of immunotherapies,” Emmanuel Derivery, Ph.D., co-author of the study, explained in a statement. “In fact, when antibody drugs bind to their target receptors and then enter and contaminate, more antibodies must always be ingested. ”
To overcome this problem, the researchers designed two protein parts that can themselves accumulate in large, flat patches. Signal molecules can then be embedded into the protein scaffolds. Using two or more genetically modified materials made the structure more controlled than those made from a single component, they said.
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The team showed that the protein fragments can move to living cells, activate surface receptors and stimulate downstream signaling. Changing the signaling molecules allows the child to target different surface receptors to work on different cell types, the researchers said.
More importantly, the child appeared to have resisted cell infiltration, and the size of the implant could be altered to last for hours or even days by change the size of the patch, according to the bioengineers.
Modified proteins have been shown to be treated alone or as drug compounds. David Baker of the University of Washington, Ph.D., co-author of another current study, co-authored a synthetic protein that could be turned on and off to reduce proteins of interest as he handled locks from cells the cells. environment. The team suggests that the technology, known as degronLOCKR, could allow treatments to be delivered at the right time in the right amount.
The ability of the new 2D protein fragments to block endocytosis may help extend the efficacy of pathway antagonists, the researchers suggested. And, “the ability to accumulate proteins designed around cells opens up new approaches to reducing immune responses to implanted cells, for example in treatment for Type 2 diabetes. 1, ”they wrote in the study.