Newswise — ROCHESTER, Minn.: Adding messenger RNA therapy improves response to cancer immunotherapy in patients who have not responded to treatment, a Mayo Clinic study reveals. Immunotherapy uses the immune system to prevent, control, and kill cancer. The study was published in Cancer Immunology Research , a journal of the American Association for Cancer Research.

The public became familiar with the term messenger RNA and its acronym mRNA during the COVID-19 pandemic. Messenger RNA vaccines work against COVID-19 by instructing cells in the body to make a protein that triggers an immune response against the virus.  

Messenger RNA technology is also of interest to cancer researchers and clinicians, as one of the biggest obstacles in cancer treatment is the low response rate in patients receiving immune checkpoint inhibitors to prevent cancer from developing. immune response is so strong that it destroys healthy cells in the body.

'We found that by introducing messenger RNA into immune cells, useful proteins are produced that enhance antitumor activity, but do not attempt to change the genome itself. This approach could perhaps be applied across the field of medicine to convert information from single-cell RNA sequencing into messenger RNA-based therapies, ”says Dr. Haidong Dong , an cancer researcher at Mayo Clinic.

In order to carry out the study, the first thing that Dr. Dong and his team did was to produce in the laboratory an immune system protein (a monoclonal antibody) capable of detecting the protein level in tumor tissues. The purpose was to determine whether the immune cells that react to the tumor had an adequate protein level in certain patients, as a possible biomarker for this therapeutic intervention.

'Current immune checkpoint inhibitor therapy does not benefit the majority of patients with advanced cancer; But our study provides a way to detect this problem and, in addition, a therapy based on messenger RNA to solve it, ”explains Dr. Dong.

The researchers then employed new sequencing technology, which makes messenger RNA-based switching possible within primary immune cells. They identified the target gene in single-cell RNA sequencing data sets, and then did a functional test to validate the role the target gene plays in enhanced immune cell-mediated killing of tumor cells.

The analysis showed a weak spot in the T cells of the patients who did not respond to immunotherapy. T cells are white blood cells that play an important role in the immune system, attacking cancer cells and preventing cancer from spreading to other places in the body. The researchers developed a messenger RNA-based strategy to improve T-cell response to immune checkpoint inhibitors in patients who did not respond to treatment.

According to Dr. Dong, the study represents a new translational method to take the information obtained in single-cell RNA sequencing studies and convert it into messenger RNA-based therapies for clinical use.  

Future research goals include optimizing protein detection tests in human tumor tissues. This will allow determining any correlations with cancer prognosis and response to immunotherapy, as well as exploring a platform for using messenger RNA in T-cell therapy.

“At Mayo Clinic, one way to pay attention to patients' needs is to offer them something new that they can't get anywhere else; therefore, we are committed to finding alternatives for patients who do not respond to current immunotherapy, ”notes Dr. Dong.

 

Financing

The study was funded by Precision Biomarker Immunotherapy (IMPRESS) and high-definition therapeutic programs from the Mayo Clinic Center for Personalized Medicine, the Mayo Clinic Center for Biomedical Discoveries, the David F. . and Margaret T. Grohne for Immunology and Immunotherapy from the Mayo Clinic Cancer Center, the Richard M. Schulze Family Foundation, and the Mayo Clinic Office for Translation into Practice Innovation Accelerator Award program that belongs to the Center for Clinical and Translational Sciences (CCaTS).

 

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Information about Mayo Clinic

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Contact for the media:

Colette Gallagher, Mayo Clinic Public Relations, [email protected]

Journal Link: Cancer Immunology Research