Researchers at the Huntsman Cancer Institute (HCI) at the University of Utah (U of U) report on a novel way to treat cancers such as multiple myeloma, using chimeric antigen receptor (CAR) T cell therapy. By using mouse models and tumor cells from patients, the team developed CAR T cells that target the CD229 molecule—present on the cancer cells of patients with myeloma—and patients displayed promising results for this novel cellular immunotherapy for multiple myeloma and other blood cancers.
The second most common blood cancer, this disease develops in the bone marrow. Around 30,000 new cases are diagnosed each year. In nearly all the cases, most eventually succumb to the disease. Multiple myeloma patients presently face a 5-year survival rate of 50%. Far too many patients with multiple myeloma relapse after treatment. Hence, the Utah-based investigators’ mission for an effective cell-based treatment ensues.
What are Immunotherapies?
Immunotherapies activate a patient’s own immune system to fight their cancer. These emerging therapies have proven to be highly effective for many types of blood cancers. In CAR T cell therapy, doctors take T cells from a patient’s blood and engineer them to recognize and attack cancer cells via an added “hook”, called a CAR, that recognizes a surface molecule on cancer cells. Engineered CAR T cells are returned to patients via intravenous infusion. The CAR T cells then find, attack, and destroy cancer cells in the patient’s body. While these approaches have demonstrated remarkable progress and long-term results for some, many patients experience only brief improvement, followed by recurrence of their disease.
The Huntsman Cancer Institute Study
Led by professor Djordje Atanackovic, MD, a physician-scientist who cares for patients with multiple myeloma, this study advanced on earlier work by Atanackovic and colleagues in which they identified CD229 as present on multiple myeloma and other B cell cancer cells. Once the CD229 target had been identified, it took several years to complete the complicated engineering and laboratory work to test whether CD229 was a viable new agent for a CAR T approach. The study extends work Atanackovic began in the lab of Lloyd Old at Memorial Sloan-Kettering Cancer Center. The HCI study was recently published in journal Nature Communications.
Dr. Atanackovic emphasized why this research has taken years describing that the current immunotherapies can work well for some patients however they were “dismayed” that many of these patients then relapse “as early as one year after treatment.” The challenge became more complicated in that they realized that they needed to target each and every cancer cell in a patient’s body, “including the cancer stem cell.” He commented, “this could make a difference and yield more durable, deeper responses to treatment.”
Designing the Therapy
The HCI-based team included Tim Luetkens, MD (protein engineering expert) and Sabarinath Radhakrishnan, MD (assist. Professor of internal medicine) who led the development of the novel therapy in Atanackovic’s lab. They engineered the first fully human antibody against CD229 and, with this newly engineered “hook,” produced CAR T cells targeting CD229. They confirmed their hypothesis CD229 CAR T kills mature multiple myeloma cells, as well as myeloma stem cells, using a mouse model, as well as stem cells derived from myeloma patients. They also evidenced that at least in this laboratory setting, the tumors treated with CD229 CAR T appeared to result in long-lasting responses.
The study was funded by the National Institutes of Health, the International Myeloma Foundation, the National Comprehensive Cancer Network Young Investigator Award, the American Association of Cancer Research, the University of Utah, including a Joseph Quagliana, MD Fellowship Award, and Huntsman Cancer Foundation.
Huntsman Cancer Institute at University of Utah
Huntsman Cancer Institute (HCI) at the University of Utah is the official cancer center of Utah. The cancer campus includes a state-of-the-art cancer specialty hospital as well as two buildings dedicated to cancer research. HCI treats patients with all forms of cancer and is recognized among the best cancer hospitals in the country by U.S. News and World Report. As the only National Cancer Institute (NCI)-Designated Comprehensive Cancer Center in the Mountain West, HCI serves the largest geographic region in the country, drawing patients from Utah, Nevada, Idaho, Wyoming, and Montana. More genes for inherited cancers have been discovered at HCI than at any other cancer center in the world, including genes responsible for hereditary breast, ovarian, colon, head, and neck cancers, along with melanoma. HCI manages the Utah Population Database, the largest genetic database in the world, with information on more than 11 million people linked to genealogies, health records, and vital statistics. HCI was founded by Jon M. and Karen Huntsman.
· Djordje Atanackovic, MD
· Tim Luetkens, MD
· Sabarinath Radhakrishnan, MD
Call to Action: The HCI-based team (at University of Utah) seeks to better understand this approach and further the potential of CD229 as a novel therapy for multiple myeloma. They will accomplish this with further analyses to determine it can be safely used in humans. Thereafter, they hope to move the treatment out of the lab and into clinical trials. TrialSite News monitors this research with hopes that it moves into clinical trials. Sign up for the daily newsletter for updates.