New mRNA-Based Therapy Effective in Treating Melanoma in Mouse Models

Investigators at the Icahn School of Medicine at Mount Sinai have designed an RNA-based strategy to activate dendritic cells, which play a key role in immune response, that eradicated tumors and prevented their recurrence in mouse models of melanoma. The findings suggest that the approach has the potential to be effective against tumors that have already spread to other parts of the body and against different cancer types.

Cancer cells employ strategies to switch off various stages of the cancer-immunity cycle, the process by which dendritic cells educate T cells to kill cancer cells. This immunosuppressive environment that impedes activation of cancer-killing T cells allows tumors to grow. As part of the regimen, the researchers used new types of lipid nanoparticles to deliver two mRNA therapeutics to ensure the dendritic cells were sufficiently activated to enhance the cancer-immunity cycle in established tumors.

The researchers named their approach CATCH. Using multiple bioassays to gain insights on the effects of the CATCH regimen on different types of immune cells, the researchers showed their strategy not only reactivated the cycle but also removed obstacles at other stages. This caused a change in the tumor’s microenvironment, shifting it from having cell types that weaken T cells’ ability to fight cancer to having cell types that actually support and enhance their ability to fight tumors.

Beyond the positive findings in mouse models of melanoma, the researchers conducted further tests to evaluate the effectiveness of the CATCH regimen in restarting the cancer immunity cycle more broadly. Their investigations revealed encouraging results, as the regimen reduced tumors in mouse models of B cell lymphoma by 83 percent. They also tested it in mouse models of breast cancer, where approximately half of the mice favorably responded.

Next, the researchers plan feasibility and safety testing for using the CATCH regimen in early-phase clinical trials for patients.

“Dendritic cells have been a key focus for the development of new cancer therapies as these cells organize the cancer-immunity cycle. In theory, the CATCH regimen using this particular RNA-based technology has the potential to provide a much more effective approach for using dendritic cells for cancer immunotherapy to treat a wide range of solid tumors,” said Brian Brown, PhD, director of the Icahn Genomics Institute and associate director of the Marc and Jennifer Lipschultz Precision Immunology Institute at Icahn Mount Sinai.