An innovative new immunotherapy treatment at the Yale Cancer Center and Smilow Cancer Hospital called CAR T-cell therapy has shown remarkable success in treating certain blood cancers, including some for which all other treatment options have failed.
“CAR T-cell therapy is a very effective treatment for childhood acute lymphoblastic leukemia, inducing remissions in about 80 percent of patients, including patients with stubborn or resistant disease,” says Dr. Stuart Seropian, co-director of the pioneering CAR T-Cell Therapy Program at Yale Cancer Center/Smilow Cancer Hospital. “These results are really astounding and have brought into question the need for stem cell transplantation, previously required for difficult-to-treat cases. Patients with leukemia or lymphoma who do not respond or relapse after conventional treatments have a poor prognosis. CAR T-cell therapy, however, has emerged as a new effective therapy that offers hope and, in some cases, has proven dramatically life-saving.”
Fellow co-director Dr. Iris Isufi and Seropian say that based on the success of the therapy thus far, many new CAR T-cell types are being developed to target other cancers.
“CAR T-cells, or Chimeric Antigen Receptor T-cells, are immune cells genetically modified to recognize and kill cancer cells,” says Seropian, explaining how the cells are used to treat certain types of non-Hodgkin’s lymphoma and childhood acute lymphoblastic leukemia, the only cancers currently approved by the FDA for treatment. “First, normal immune cells are collected from the blood of a patient and sent to a laboratory where they are modified and multiplied over the course of several weeks. They are then administered back to the patient through a transfusion. Once returned to the patient, the cells circulate in the blood, multiply and attack tumor cells to induce remission of the cancer.”
Since chemotherapy is required before treatment that could increase the risk of infection, and CAR T-cell therapy has possible side effects including fever, seizures, low blood pressure or reduced oxygen levels, patients require close observation and management by a multidisciplinary team including stem cell transplant specialists, neurologists and often intensive care specialists, Isufi says. That’s why the CAR T-cell program involved the training and education of several hundred staff members, including at Yale New Haven Children’s Hospital, where pediatric patients undergoing the T-cell therapy are treated.
Both doctors, along with Dr. Alexey Bersenev, the director of the program’s cell processing lab and leading the research side, say the possibilities of expanding the therapy to effectively treat additional cancers is promising, noting that a clinical trial will soon begin at Yale to test a new type of CAR T-cell for patients with breast cancer or certain gastrointestinal tumors.
“The scope and pace of research involving CAR T-cell therapy is remarkable,” Seropian says. “Thus far, success has been limited to lymphoblastic leukemia, non-Hodgkin’s lymphoma and multiple myeloma, which are all blood cancers. This therapy is not currently FDA-approved for multiple myeloma, but results are quite promising in clinical trials, and it’s being tested in a number of ‘solid’ tumors such as brain tumors and lung cancers.”
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