According to Mayo Clinic research, adding messenger RNA, or mRNA, therapy to cancer immunotherapy enhances responsiveness in individuals who aren’t responding to the treatment. Immunotherapy is a type of cancer treatment that makes use of the body’s immune system to prevent, control, and eliminate cancer.
Cancer Immunology Research, a magazine of the American Association for Cancer Research, published the work.
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,” says Haidong Dong, M.D., Ph.D., 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.”
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. 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.
Haidong Dong
Dr. Dong and his team created a monoclonal antibody, an immune system protein that can identify protein levels in tumor tissues, in the lab for the study.
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,” says 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. T cells were found to be poor in patients who did not respond to immunotherapy, according to the findings.
White blood cells known as T cells perform a vital part in the immune system. They target cancer cells and prevent the disease from spreading to other parts of the body.
In individuals who were not responding to immune checkpoint medications, the researchers devised an mRNA-based method 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 usage.
The goal of future study is to improve the screening technique for detecting the protein in human tumor tissues. This will aid in determining whether there is a link between cancer prognosis and immunotherapy responsiveness, as well as exploring a platform for employing 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,” says Dr. Dong. “We are committed to finding options for patients who do not respond to current immunotherapy.”
