CAR-T细胞 z-bo 2020-09-30 328

　　Most patients with cancers such as multiple myeloma will relapse after treatment. This harsh reality has prompted scientists to try to improve the depth and durability of the treatment response in multiple myeloma through a new cancer cell targeting mechanism. Multiple myeloma is the second most common type of blood cancer and occurs in the bone marrow. Approximately 30,000 new cases are diagnosed each year, and almost all patients eventually die from the disease.

　　In a new study, researchers from the University of Utah and other research institutions described a new method of using chimeric antigen receptor (CAR) T cell (CAR-T) therapy to treat cancer. Laboratory tests using mouse models and tumor cells from patients have shown that this new cellular immunotherapy has shown promising results in the treatment of multiple myeloma and other types of blood cancers.

　　These researchers developed CAR-T cells that target the CD229 molecule. This molecule is present on the surface of cancer cells in patients with myeloma throughout the course of the disease. Importantly, CD229 is also present on the surface of myeloma stem cells, which are the source of treatment-resistant tumor cells in relapsed patients.

　　Immunotherapy that activates the patient’s own immune system to fight against their cancer has been proven to be very effective against many types of blood cancers. In CAR-T cell therapy, doctors obtain T cells from the patient's blood, and then genetically modify them so that they express CARs that recognize molecules on the surface of cancer cells, so that they can recognize and attack cancer cells. The genetically modified CAR-T cells are infused back into the same patient by intravenous injection. These CAR-T cells then discover, attack and destroy cancer cells in cancer patients. Although this approach has shown significant progress and long-term effects for some patients, many patients only experience short-term improvements, and then their disease relapses.

　　This study was led by Dr. Djordje Atanackovic, associate professor of internal medicine in the Department of Hematology and Hematological Malignancies, University of Utah. This study is based on the early work of Atanackovic and his colleagues: They have identified CD229 on the surface of multiple myeloma cells and other B-cell cancer cells. Once the target CD229 was identified, they spent several years completing complex laboratory work to test whether CD229 is a viable new target for CAR-T cell therapy.

　　Atanackovic said, "We are frustrated that although some of our patients respond well to currently available immunotherapies, they relapse within a year after treatment. We think if we can target every cancer cell in the patient , Including cancer stem cells, then this may make a crucial difference and produce a longer-lasting and deeper treatment response."

　　Dr. Tim Luetkens, an expert in cell and protein engineering at the University of Utah, and Dr. Sabarinath Radhakrishnan, an assistant professor of internal medicine at the University of Utah, led the development of this therapy in the Atanackovic laboratory. They designed the first fully human antibody against CD229 and used this designed antibody to construct CAR-T cells that target CD229. They confirmed that CD229 CAR-T cells kill mature multiple myeloma cells and myeloma stem cells in mouse models and cancer stem cells from myeloma patients. They also found that under such laboratory conditions, myeloma treated with CD229 CAR-T cells seemed to produce a durable immune response.

　　These researchers plan to conduct further analysis to understand whether this method can be safely used in humans. They hope to conduct clinical trials to further understand the potential of CD229 as a new treatment for multiple myeloma.