Cancer Cell: The "eat me" marker that translates cancer genes into the immune system

It is well known that tumor cells are good at hiding from the body's immune system; They build physical barriers, wear camouflage, and handcuff the immune system

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 was considered incurable — though it's very common

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 found that when ars1620, a sotorasibi-like targeted KRAS drug, binds to mutant KRAS, it not only prevents KRAS from affecting tumor growth

"This mutated protein is usually unknown because it's 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

More research

The new approach paves the way not only for combination therapies for KRAS-mutant cancer, but also for pairing other similar targeted drugs with immunotherapy, the researchers

"It's a platform technology," Craik said
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"We want to look for other targets that may also move molecules to the surface of cells, adapting them to immunotherapy
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