Individualized cancer therapy demonstrates safety and sustained immune responses
Source: Eurek Alert!, August 2024
For decades, researchers have worked to develop therapies that can prime the immune system to recognize and attack proteins on the surface of tumor cells. However, success has been limited due to the technological challenge of engineering therapies that provide specific enough “training” to the immune system to identify a given patient’s neoantigens. Now, investigators from Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system, have evaluated an investigational, individualized neoantigen therapy (INT), containing patient-specific mRNA-encoded instructions that the immune system can use to target cancer-causing cells. Their results highlight the safety, feasibility, and therapeutic promise of the approach, which has been designated breakthrough status by the U.S. Food and Drug Administration (FDA) to accelerate further clinical research. The study was published in Cancer Discovery, a journal of the American Association for Cancer Research.
“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 MGH. “While it may sound like science fiction, 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.”
The Phase 1 study (NCT03313778), sponsored by Moderna, Inc., in collaboration with Merck, known as MSD outside of the United States and Canada, evaluated a novel INT called mRNA-4157 (V940). The trial included 16 patients, four with resected non-small cell lung cancer and 12 with resected cutaneous melanoma. The researchers performed comprehensive genomic sequencing of each patient’s tumor to determine their top neoantigens, up to 34 of which were then encoded in each mRNA therapy. Therapies and vaccines that use mRNA can produce robust immune responses and are optimal for individualized cancer therapies because the mRNA corresponding to the patient’s neoantigens can easily be inserted into the therapy’s delivery system.