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When cancer immunotherapy fails, this new therapy may help, Mayo Clinic study shows

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Patients who didn’t respond to cancer immunotherapy can get better results by adding messenger RNA, or mRNA therapy, says a new Mayo Clinic study.

Immunotherapy is a type of cancer treatment that makes use of the body’s immune system to prevent, control, and eliminate cancer.

The work was published in Cancer Immunology Research.

During the COVID-19 pandemic, the terms messenger RNA and its acronym, mRNA, became widely known. COVID-19 mRNA vaccines function by telling the body’s cells how to generate a protein that causes an immune response against the virus.

Cancer researchers and clinicians are also interested in MRNA technology. The low response rate in patients who get immune checkpoint inhibitors, which prevent an immune response from becoming so strong that it destroys healthy cells in the body, is one of the greatest challenges in cancer treatment.

“We found that by introducing mRNA in immune cells, it is possible to produce useful proteins to improve their anti-tumor activity without attempting to change the genome itself,” said Dr. Haidong Dong.

“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.”

For the study, Dr. Dong and his team created a monoclonal antibody, an immune system protein that can identify protein levels in tumor tissues. The goal was to see if adequate protein levels in tumor-reactive immune cells may be used as a diagnostic for this therapeutic intervention in particular patients.

“Most patients with advanced cancers have not benefited from current immune checkpoint blockade therapy,” added Dr. Dong.

“Our study provides a tool to detect this problem and also provides a mRNA-based therapy to fix it.”

The researchers then used a novel sequencing technique that allows for mRNA-based changes in primary immune cells. In single-cell RNA-sequencing datasets, they found the target gene. They next ran a functional test to confirm the target gene’s role in increased immune cell-mediated tumor cell killing.

In individuals who did not respond to immunotherapy, the study revealed a weak spot in T cell. T cells are white blood cells that help the immune system work properly. They block cancer from spreading to other parts of the body by attacking cancer cells. In individuals who were not responding to immune checkpoint inhibitors, the researchers created an mRNA-based solution to improve their T cell response.

According to Dr. Dong, the work represents a unique translational technique for leveraging knowledge gathered from single-cell RNA-sequencing investigations into mRNA-based therapy for clinical use.

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

Source: Cancer Immunology Research

Image Credit: GEtty

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