Introducing mRNA (messenger ribonucleic acid) technology to cancer immunotherapy improves the response in patients who weren’t previously responding to treatment, according to new research published in the journal Cancer Immunology Research.

The term ‘mRNA’ has become well-known since the development of mRNA vaccines for Covid-19. The technology works by instructing cells in the body how to make a protein that triggers an immune response against the virus. However, where the Covid-19 vaccines are preventative, mRNA vaccines for cancer are therapeutic.

The technology tackles the low response rate in patients receiving immune checkpoint inhibitors

One of the major obstacles in cancer treatment is the low response rate in patients who receive immune checkpoint inhibitors, which prevent an immune response from being so strong that it destroys health cells in the body.

“Most patients with advanced cancers have not benefited from current immune checkpoint blockade therapy,” says Haidong Dong, M.D., Ph.D., a Mayo Clinic cancer researcher. "Our study provides a tool to detect this problem and also provides a mRNA-based therapy to fix it."

The researchers at the Mayo Clinic produced an immune system protein in the lab ― a monoclonal antibody ― that can detect the protein levels in tumour tissues. The goal was to determine whether certain patients may have appropriate protein levels in their tumour-reactive immune cells as a potential biomarker for this therapeutic intervention.

Next, the researchers employed new sequencing technology that makes a mRNA-based change of primary immune cells possible. They identified the target gene in single-cell RNA-sequencing datasets, then they performed a functional test to validate the role of the target gene in enhanced immune cell-mediated killing of tumour cells.

The analysis indicated a weak spot of T cells (which are white blood cells that play an important role in the immune system) in patients who did not respond to immunotherapy. They attack cancer cells and stop the cancer from spreading to other sites of the body.

The researchers then developed a mRNA-based strategy to improve their T cell response to immune checkpoint inhibitors in patients who weren't responding to the treatment.

The approach “may have the potential to be used across the spectrum of medicine”

The study models a new translational approach to leverage information gained from single-cell RNA-sequencing studies into mRNA-based therapy for clinical use, according to Dr Dong.

The team now hope to optimise the screening test to detect the protein in human tumour tissues, which will help to determine any correlation with cancer prognosis and responsiveness to immunotherapy.

Dr Dong says the approach “may have the potential to be used across the spectrum of medicine to pull information gained from single-cell RNA-sequencing into mRNA-based therapy for patients.”