Scientists have developed a drug that overcomes some of the barriers that cancer cells put up to escape from the human immune system and helps these cells recognize infected cells to destroy them.
The new drug, developed by a group of scientists from the University of California, San Francisco (UCSF), captures the mutant version of the KRAS protein on the surface of cancer cells, where the KRAS compound acts as a marker and says: “I ate.”
Then, immunotherapy can encourage the immune system to effectively kill any cells that carry this marker.
A researcher at the Howard Hughes Medical Institute, UCSF chemist Dr. “The immune system has the ability to recognize the mutated hard gene, but it’s usually not very good,” said Kevan Shokat. Easier for the immune system. “
Mutations in the hard gene are found in up to 25% of all tumors in humans. This makes it one of the most common genetic mutations in cancer.
The problem is that Keras has traditionally been difficult to machine for various reasons, including for example its surface – it is too “smooth” for drug molecules to stick.
In the new study, scientists are looking for a way to target other inappropriate features of Keras because it looks like a healthy version when mutated and moves inside cells rather than on the surface, which making it harder for the immune system to recognize mutations. .
The team discovered that a drug called ARS1620 can help solve these two problems, because the molecule binds well to the mutated “cherry” protein and not only prevents this protein from affecting the growth of tumor, but also attracts protein to the cell surface. There, the protein and drug combine and send a signal that directs the immune system to attack.
The study’s lead author and professor of pharmaceutical chemistry at the University of San California, Dr. “It’s exciting to have a new approach so we can harness the immune system and combine it with targeted drugs in Keras,” said Charles Crick. Francisco.
For years, Keras was considered incurable despite its prevalence in cancers. The mutated version of the protein that makes cancer cells grow often works inside cells with a slight change that differentiates it from the normal hard gene, and there is no clear point in its structure that allows the drug to bind. IT.
In recent years, however, Forks conducted detailed analyzes of the protein and discovered a hidden pocket in the mutated “cherry” that could be blocked by any drug. His work contributed to the development and approval of sotorasib.
However, sotorasib does not help all patients with Keras mutations, and some tumors that shrink become resistant and start growing again.
Shokat, Crick, and their colleagues wondered if there was another way to target Keras.
Through the new study, the team showed that when ARS1620 binds to mutated ‘KRAS’, it not only prevents KRAS from affecting tumor growth, but also convinces the cell to recognize the ARS1620-KRAS complex as a foreign molecule.
In studies on both isolated proteins and human cells, the scientists showed that the most promising antibodies identified during the study could bind tightly to ARS1620 in addition to ARS1620-KRAS complex.
The group then developed an immunotherapy around this antibody, allowing the T cells of the immune system to recognize the Kiras marker and target the cells for destruction. They found that the new immunotherapy can kill cancer cells that contain ARS1620 mutations, including those that have developed resistance to ARS1620.
“What we’ve shown here is proof of principle that a cell resistant to existing drugs can be killed by our approach,” Shokat said.
More studies in animals and humans are needed before the treatment can be used clinically.
Source: Medical Express
Source: Arabic RT
