Researchers at the Icahn School of Medicine at Mount Sinai have discovered a way to move precision immunotherapy forward by using genomics to inform immunotherapy for multiple myeloma, a blood cancer, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, in December.
This is the first study to experimentally determine which byproducts from the mutation of tumors (known as neoantigens) have the ability to provoke the immune system into recognizing and killing cancer cells in multiple myeloma patients. The results provide the foundation for using neoantigen-targeting strategies such as cancer vaccines in future trials for multiple myeloma patients. Multiple myeloma is a malignancy of plasma cells affecting 30,000 people a year.
Next-generation sequencing data was analyzed to describe the landscape of neoantigens in 184 patients, and researchers identified neoantigen-specific immune cells triggered by immunotherapy. Additionally, they showed an increase in neoantigens in patients who had relapsed myeloma versus new patients, which may indicate potential for greater immune responses to immunotherapy in these patients. The study also identifies common neoantigens between patients, which could lead to new vaccine therapies.
"Tumor neoantigens represent excellent targets for immunotherapy, due to their speci?c expression in cancer tissue," said Samir Parekh, MD, Associate Professor of Oncological Sciences and Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine. "Until now, there has been no direct evidence that DNA mutations induce neoantigen-speci?c T-cell responses following immunotherapy in multiple myeloma."
Stemming from this research, co-author Nina Bhardwaj, MD, PhD, Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine, and colleagues are pursuing a clinical trial investigating the safety and responsiveness of a personalized neoantigen vaccine for the treatment of cancers including multiple myeloma.
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This study was supported by the NIH (R21 CA223953) and the Multiple Myeloma Research Foundation.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology, Mount Sinai St. Luke's and Mount Sinai West are ranked 23rd nationally for Nephrology and 25th for Diabetes/Endocrinology, and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.
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Journal
Clinical Cancer Research