Immunotherapy drug marks cancer cells for destruction

A novel immunotherapy drug blocks tumour growth and marks cancer cells for destruction by the immune system, new research suggests.

Researchers from the University of California San Francisco (UCSF) have developed an immunotherapy drug, ARS1620, to target mutated KRAS proteins. Mutations in the KRAS gene are implicated in approximately 25 percent of all tumours.

Dr Kevan Shokat, co-corresponding author and study co-lead stated: 'The immune system already has the potential to recognise mutated KRAS protein, but it usually can't find it very well. When we put this marker on the protein, it becomes easier for the immune system.'

However, treatment of mutated KRAS protein is difficult as the mutation that drives the growth of tumour cells operates inside the cell. The cell surface of mutated KRAS proteins is smooth, making it difficult for drug molecules to bind, and easy for the tumour to evade detection by the body's immune system.

In a paper published in Cancer Cell, the researchers detailed the process whereby ARS1620 binds to mutated KRAS protein and pulls the protein out to the cell surface. The drug and the protein then form an ARS1620-KRAS complex which acts as a marker, sending a signal to the immune system to alert it to attack.

Several human antibodies were screened during the drug development process, and researchers were able to demonstrate (in both isolated protein and human cells) that they had identified the best antibody to bind to ARS1620, as well as the ARS1620-KRAS complex. When tested in lung cancer cells, cancer growth was inhibited by 82 percent, compared with just 44 percent in the untreated cells.

'It's exciting to have a new strategy leveraging the immune system that we can combine with targeted KRAS drugs,' said Professor Charles Craik, the second corresponding author of the paper and study co-lead at UCSFC. 'We suspect that this could lead to deeper and longer responses for cancer patients.'

Before this treatment can be clinically approved, further research in animals and humans must be conducted. The results of which could pave the way for combination treatments in cancers with KRAS mutations, as well as other pairings of targeted drugs with immunotherapies.

'This is a platform technology,' Professor Craik added. 'We'd like to go after other targets that might also move molecules to the cell surface and make them amenable to immunotherapy.'