Immune system responds to mRNA treatment for cancer: Study

According to a new study by the Mayo Clinic, mRNA therapy improves the response to cancer immunotherapy in patients, who weren't responding to the treatment.

The research has been published in the 'American Association for Cancer Research Journal'.

The phrase messenger RNA and its acronym, mRNA, had become familiar to the public during the COVID-19 pandemic. The mRNA vaccines for COVID-19 worked by instructing cells in the body how to make a protein that triggers an immune response against the virus.

mRNA technology had also been of interest to cancer researchers and physicians. One of the major obstacles in cancer treatment is the low response rate in patients who received immune checkpoint inhibitors to prevent an immune response from being so strong that it destroyed healthy cells in the body.

"We found that by introducing mRNA in immune cells, it is possible to produce useful proteins to improve their anti-tumour activity without attempting to change the genome itself," said Haidong Dong, M.D., PhD, a Mayo Clinic cancer researcher.

"This 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," Dong added.

For the study, Dr Dong and his team produced an immune system protein in the lab. A monoclonal antibody that could 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.

"Most patients with advanced cancers have not benefited from current immune checkpoint blockade therapy," said Dr Dong.

"Our study provides a tool to detect this problem and also provides an mRNA-based therapy to fix it," Dong added.

Next, the researchers employed new sequencing technology that made an 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 the enhanced immune cell-mediated killing of tumour cells.

The analysis indicated a weak spot of T cells in patients who did not respond to immunotherapy. T cells are white blood cells that play an important role in the immune system. They attack cancer cells and stop cancer from spreading to other sites of the body. The researchers developed an mRNA-based strategy to improve their T cell response to immune checkpoint inhibitors in patients who weren't responding to the treatment.

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.

Future research goals include optimizing the screening test to detect the protein in human tumour tissues. This will help to determine any correlation with cancer prognosis and responsiveness to immunotherapy and explore a platform for using mRNA for T cell therapy.

"At Mayo Clinic, one way to meet the needs of patients is to offer them something new that they cannot find in other places," said Dr Dong.

"We are committed to finding options for patients who do not respond to current immunotherapy," Dong added.

( With inputs from ANI )

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