Researchers artificially generate immune cells integral to creating cancer vaccines

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(New York, NY – August 14, 2018)– For the first time, Mount Sinai researchers have identified a way to make large numbers of immune cells that can help prevent cancer reoccurrence, according to a study published in August in Cell Reports.

The researchers discovered a way to grow the immune cells, called dendritic cells, at large scale in the lab to study them for their potential use in highly refined cancer vaccines to prevent patients' cancer from coming back. Dendritic cells are very rare in the body, so it has not been possible to isolate them from patients for generating vaccines without great expense and highly complicated methods.

The ability to grow many types of dendritic cells, which act as sentinels that warn the immune system to gear up with weapons specific to the disease it is attacking, will allow researchers to study their roles in the immune system. This discovery is especially important because dendritic cells aren't limited to one type of cancer and can attack all types of cancer with very limited side effects.

"The ability to generate large numbers of distinct types of human dendritic cells in vitro is critical for accelerating our understanding of dendritic cell biology and to harness them clinically," said Nina Bhardwaj, MD, PhD, Director of Immunotherapy at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "Our system will also be useful for translational applications including in vitro drug and vaccine testing on different dendritic cell types."

This study also investigated the role of notch signaling, which is a biological pathway that plays a critical role in the development of a variety of organisms, from flies to humans, and is critical for generating a specific type of dendritic cell, cDC1, that is the best type of dendritic cell for cancer vaccines. The study revealed that some of the current cancer treatments being tested in clinical trials are flawed because they disrupt the notch signaling pathway, which could inhibit cDC1 and thus may negatively affect the immune system's ability to kill cancer cells.

This research is a jumping-off point for further research on the different types of dendritic cells and other immune cells and has implications for not only boosting cancer-fighting therapies but also to prevent organ transplant rejection, which involves the immune system as well.

This study furthers Dr. Bhardwaj's work with dendritic cells and vaccine development. Dr. Bhardwaj, a leader in this field, heads Mount Sinai's Vaccine and Cell Therapy Laboratory, which prepares cell-based protein and peptide-based vaccines. Dr. Bhardwaj's expertise in this area has been widely recognized, most recently by being invited by the Parker Institute for Cancer Immunotherapy to participate in collaborative research with scientists from nine top medical centers around the country.

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The study was performed in collaboration with Marc Dalod, PhD, of Centre d'Immunologie de Marseille-Luminy in Marseille, France. Sreekumar Balan, PhD, a post-doctorate researcher at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, also played a significant role in this research.

This work was supported by the I2HD CIML-SANOFI project, Inserm, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS project ECTZ25472), the DCBIOL Labex (ANR-11-LABEX-0043, grant ANR-10-IDEX-0001-02 PSL) and the A*MIDEX project (ANR-11-IDEX-0001-02) funded by the French Government's "Investissements d'Avenir" program managed by the ANR, the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement 281225; to M.D.); the NIH (AI044628, CA180913 and AI081848), the Cancer Research Institute and the Melanoma Research Alliance.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, 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 System includes approximately 6,600 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 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. 13 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. 18 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, Nephrology, and Neurology/Neurosurgery, and in the top 50 in four other specialties in the 2017-2018 "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 and 50th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.

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