Researchers at Peter Mac have identified a new type of immunotherapy in solid tumours that tricks cancer cells into alerting our own immune system to destroy them.
The research, published in Cancer Discovery in collaboration with Storm Therapeutics, uses a world-first drug that targets mRNA.
The drug modifies cancer cells to make them behave as though they have been infected with a virus causing them to send signals to the immune system which triggers a response to destroy the cancer cells.
Professor Mark Dawson, Consultant Haematologist at Peter Mac and Royal Melbourne Hospital, Head Cancer Biology and Therapeutics Program and Head Cancer Epigenetics Laboratory at Peter Mac, said because the immune system doesn’t easily recognise cancer cells as dangerous, we needed to find a way to make the immune system sit up and notice the cancer cells.
“We identified that when the enzyme (METTL3) was inhibited in cancer cells, a specific chemical modification of RNA (called m6A) is lost, resulting in a new structure that resembles an RNA virus,” he said.
“As a result, the immune system believes the cancer cells are being attacked by a virus and they get to work seeking out the ‘infected’ cancer cells to destroy them.”
This exciting development is a new way of treating cancer cells that may evade existing anti-cancer immunotherapies such as immune checkpoint inhibitors like anti-PD1. In fact, when the METTL3 inhibitor are combined with these existing immunotherapies they are even more effective.
Oliver Rausch, Chief Scientific Officer of STORM Therapeutics and joint senior author of the study, said, “this novel approach is a result of Storm Therapeutics developing a first in class drug targeted at the METTL3 enzyme that lays down m6A, the most abundant chemical modification on mRNA.
“We worked with researchers at Peter Mac to help us identify how this new drug could be used as an anti-cancer therapy.
“These positive preclinical results are very exciting and we are now embarking on clinical trials with this brand new treatment in patients with solid tumours.”
This exciting research was made possible at Peter Mac with the support of a mRNA Victoria grant, which has assisted with part of the current research project and ongoing work that has stemmed from this finding.
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