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The new therapy, published Sept.
"The immune system already has the ability to recognize mutated KRAS, but it usually doesn't detect it
KRAS mutations are found in about a quarter of tumors, making it one
"It's exciting to have a new strategy that harnesses the immune system and we can combine drugs that target KRAS," said Dr.
Flip out the cancer markers
The immune system is usually able to recognize foreign cells because unusual proteins
For years, KRAS — though it's very common in cancer — was considered incurable
However, Sotorasib doesn't help all patients with KRAS mutations, and some of the tumors it shrinks down develop resistance and start growing
In the new study, the team showed that when ARS1620, a KRAS-targeted drug similar to sotorasib, binds to mutant KRAS, it not only prevents KRAS from affecting tumor growth
Craik said: "This mutated protein is usually unknown because it is very similar
This means that the cell processes the protein and transfers it to the cell surface as a signal
A promising immunotherapy
As the mutated KRAS is transferred from within the cell to the outside, the UCSF team is next able to sift through billions of human antibody libraries to identify those that can now recognize the KRAS marker
The team then designed an immunotherapy around this antibody that induces the immune system's T cells to recognize the KRAS marker and destroy the target cells
Shokat said: "What we are showing here is the proof of principle that our strategy can kill cells
Ziyang Zhang, Peter J.