mRNA Cancer Therapy Boosts Immune Response

An investigational, individualized neoantigen therapy, with personalized encoded mRNA, has demonstrated potential to enable patients’ immune systems to target cells that cause cancer.

The Phase I study evaluated the novel therapy mRNA-4157 (V940) in 16 patients, four of whom had resected non-small cell lung cancer and 12 of whom had resected cutaneous melanoma. The researchers encoded the patients’ top neoantigens into each mRNA therapy. Melanoma patients were treated with both mRNA-4157 (V940) and the immune checkpoint inhibitor pembrolizumab.

Analysis from the study revealed mRNA-4157 (V940) “induced multiple forms of T cell proliferation, both alone and in conjunction with pembrolizumab.” mRNA-4157 (V940) treatment was not associated with dose-limiting toxicity. The findings point to the long-term potential of the mRNA therapy. T-cell response to neoantigens was found to remain 30 weeks posttreatment, according to study data. The low toxicity of mRNA-4157 (V940) could help simplify “combining individualized neoantigen therapies and other immunotherapies,” explained the researchers.

“We are entering an era in which we have the tools to make cancer therapies more precise and more personalized,” said corresponding author Justin Gainor, MD, program director of the Center for Thoracic Cancers at Massachusetts General Hospital. “We’ve shown that we can develop an individualized neoantigen therapy by leveraging the specific characteristics of a given patient’s tumor and cell type. This therapy was both safe and immunogenic, meaning that we were able to amplify existing responses and induce brand-new, long-lasting immune responses.”     ❖