【Cancer Cell】Breakthrough! New Approach Makes KRAS Cancer Genes Say 'Eat Me' to the Immune System

This article is the original of the translational medicine network, please indicate the source when reprinting

Author: Lily

Tumor cells are known to be very cunning, and they are adept at evading the human immune system — for example, building physical barriers, putting on disguises, or using molecular tricks to disable the immune system

On September 12, UCSF researchers published a research paper titled "A covalent inhibitor of K-Ras (G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy" in the prestigious journal Cancer Cell

Kevan Shokat, one of the study's leading leaders, UCSF chemist and Howard Hughes Medical Institute researcher, said: "Normally, the immune system is not very effective at recognizing these mutated KRAS

Mutation KRAS is one of the most common genetic mutations in cancer, and it is present in a quarter of tumors

Another lead study author, Dr.

Pull cancer markers from inside the cell to outside the cell

 01 

The immune system is usually effective at recognizing foreign cells because unusual proteins protrude

For many years, although KRAS was common in cancer, it was considered incurable

However, the drug sotorasib does not help all patients with

In their new work, the research team showed that when ARS1620, a targeted KRAS drug similar to Sotolasi, binds to the mutated KRAS, it not only prevents KRAS from aiding tumor growth, but also induces cells to recognize the ARS1620-KRAS complex as a foreign molecule

"This mutated protein usually flies under radar because it's very similar to a healthy protein," Dr.

Biopsy of lung tumor under microscopic observation

A promising immunotherapy

 02 

As the mutated KRAS moves from inside the cell to the outside, the research team is next able to sift through a library of billions of human antibodies to identify those that can now recognize the KRAS mark

The team then devised an immunotherapy around that antibody to induce the immune system's T cells to recognize the KRAS marker and target cells for destruction

The researchers say the new approach could pave the way not only for combination therapy for cancers with KRAS mutations, but also for targeted drugs to other similar pairings of immunotherapy

Dr Shokat said: "What we are showing here is a proof of principle that our strategy can kill cells

Resources:

https://medicalxpress.
com/news/2022-09-drug-cancer-gene-flag-immune.
html

Note: This article is intended to introduce medical research advances and cannot be used as a reference for
treatment options.

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