Mount Sinai Researchers Make Immunotherapy Work for Treatment-Resistant Lymphoma
Transplanting T-Cells Boosts Efficacy of Immunotherapies in Several Cancers
Mount Sinai researchers have developed a way to use immunotherapy drugs against treatment-resistant non-Hodgkin’s lymphomas for the first time by combining them with stem cell transplantation, an approach that also dramatically increased the success of the drugs in melanoma and lung cancer, according to a study published in Cancer Discovery in August.
This type of immunotherapy, called “checkpoint blockade,” ramps up the ability of immune cells called T cells to fight cancer by removing the “cloaking effect” that tumors use to hide from them. Checkpoint blockade therapy is effective in several tumor types, but generally ineffective in non-Hodgkin’s lymphomas. However, the study found that when this immunotherapy is combined with a stem cell transplant, which the researchers call “immunotransplant,” the process ramps up the T cells to increase the cancer-killing immune response tenfold, allowing it to be effective for non-Hodgkin’s lymphoma and more successful for melanoma and lung cancer.
The transplant works by "making space" for re-infused immune cells (T cells) to proliferate by clearing out a patient’s original immune system. While they are proliferating and building the immune system back up, they become activated, and the anti-tumor T cells’ anticancer effect becomes stronger.
The findings have prompted the initiation of a clinical trial using the immunotransplant approach to treat patients with aggressive non-Hodgkin’s lymphoma (clinicaltrials.gov/ct2/show/NCT03305445), which began enrolling patients in May. They also could eventually lead to effective therapies for other cancer types.
“Using immunotransplant to enhance the efficacy of checkpoint blockade therapy could be broadly significant as these immunotherapies are a standard therapy for melanoma, kidney cancer, lung cancer, and others,” said the study’s corresponding author Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at The Tisch Cancer Institute at Mount Sinai. “Even for settings in which checkpoint blockade therapy proves ineffective, our data suggest that its efficacy may be ‘rescued’ by immunotransplant. This research also suggests that the addition of checkpoint blockade may improve other T cell therapies, such as CAR-T therapy.”
Investigators based their findings in the study on their observation of how the immune system responded to bone marrow transplants, T cell therapy, immunotherapy, and immunotransplant in patients and mouse models.
This study was supported by The Tisch Cancer Institute’s National Institutes of Health T32 Transplant and 5T32AI078892 and T32 Immunology 5T32AI007605 training grants.
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 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.