City of Hope opens first multiple myeloma autologous CAR T cell therapy trial targeting CS1 protein on cancer cells

May 8, 2019
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Letisia Marquez
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City of Hope will manufacture CAR T cells in its own laboratories
 
DUARTE, Calif. — City of Hope is now enrolling patients with multiple myeloma whose disease has relapsed, or is treatment-resistant, for a first-of-its kind chimeric antigen receptor (CAR) T cell therapy trial.
 
The phase 1 trial is the first autologous CAR T trial to target the CS1 protein, which is expressed by cancer cells in nearly all multiple myeloma patients, said Xiuli Wang, Ph.D., City of Hope research professor in the Department of Hematology & Hematopoietic Cell Transplantation, whose team developed the CS1 CAR T and tested it successfully in preclinical and translational research. Furthermore, CS1 has a low expression on normal tissues, which is significant because those cells will not be severely damaged.
 
“CS1 is a very promising target for multiple myeloma patients who currently have few viable treatment options,” Wang said.
 
City of Hope was an early pioneer in CAR T cell therapy with research beginning in the late 1990s. It was among the first institutions in the nation to treat patients with CAR T therapies. Since then, its CAR T program has become one of the most comprehensive in the world — it is one of the largest volume centers in the nation, having treated over 300 patients since 2000, and currently has 16 open trials.
 
Multiple myeloma patients, who account for 10 percent of all blood and bone marrow cancer patients, have few treatment options. The cancer develops when plasma cells — infection-fighting blood cells in the immune system — become abnormal and grow and divide uncontrollably to become tumors.
 
Maung Myo Htut, M.D., the trial’s principal investigator and City of Hope assistant clinical professor of hematology and hematopoietic cell transplantation, explained that CAR T therapy trials currently target a different protein on multiple myeloma cells. Another treatment includes a monoclonal antibody, or chemotherapy, that can eradicate multiple myeloma cells in patients with relapsed disease, but it doesn’t always work.
 
“We expect the CS1 CAR T therapy will be even stronger than the antibody,” Htut said.
 
The study, which is a City of Hope Alpha Stem Cell Clinic trial, will enroll multiple myeloma patients who have already used three treatment options but whose disease has returned or has not responded to treatment.
 
Patients will be tested for the CS1 antigen, and, if they qualify for the trial, their T cells, a type of immune cell, will be collected intravenously during a process known as apheresis. In a City of Hope good manufacturing practice (GMP) facility, the patient’s T cells are then reengineered to express CS1 CARs, or special receptors on a cell’s surface that target the CS1 antigen. CARs are also multiplied in a lab and then infused back into the patient. The CARs are expected to multiply inside a patient’s body and better recognize and kill cancer cells.
 
“Normal T cells are ‘regular soldiers’ trying to fight cancer,” Htut added. “We modify them outside the body in the lab and make them Navy SEALs so they are more effective.”
 
City of Hope will manufacture the CAR T cells using in its own facility, the Cellular Therapy Production Center. This process includes a critical step: The patients’ T cells are reprogramed with viruses engineered in another of City of Hope’s GMP facilities, the Center for Biomedicine & Genetics. These two facilities, coupled with its Chemical GMP Synthesis Facility, make City of Hope one of the few cancer centers in the world with the ability to produce GMP cellular, genetic and drug-based therapies for its patients.
 
The trial is supported by City of Hope's Judy and Bernard Briskin Center for Multiple Myeloma Research within the Hematologic Malignancies and Stem Cell Transplantation Institute. The center is committed to aggressively pursuing and encouraging new myeloma research, developing new and improved treatments and collaborating with national and international experts.
 
Mustang Bio Inc. has exclusively licensed certain City of Hope intellectual property that relates to the CS1 CAR T cell therapy.
 
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About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked one of America's "Best Hospitals" in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on FacebookTwitterYouTube or Instagram.