CD19-targeting CAR T-cell immunotherapy yields high responses in treatment-resistant CLL
SEATTLE – Dec. Three, two thousand sixteen – In a puny, early phase trial, a high percentage of patients who had tired most traditional treatments for chronic lymphocytic leukemia eyed their tumors shrink or even vanish after an infusion of a very targeted, experimental CAR T-cell immunotherapy developed at Seattle’s Fred Hutchinson Cancer Research Center.
Fred Hutch researchers introduced their findings in an oral presentation at 7:45 a.m. Dec. Three at the American Society of Hematology Annual Meeting and Exposition in San Diego.
Almost all of the twenty four patients in the examine had cancer that had advanced despite treatment with a freshly approved drug called ibrutinib – an ominous indicator for patient survival. Most patients also had chromosomal markers in their leukemia cells that put them at high risk – “predictors of a bad response to most standard therapies,” said Dr. Cameron Turtle, a hematologist/oncologist in the Clinical Research Division at Fred Hutch who co-leads the trial with colleagues Drs. David Maloney and Stanley Riddell.
Dr. Cameron Turtle
Fred Hutch file
Turtle’s presentation will concentrate on the results in a subgroup of patients who received the CAR T-cell infusion using preferred chemotherapy and CAR T-cell doses that evolved from latest trial data. Fourteen of the nineteen restaged patients experienced a partial or accomplish regression of the disease in their lymph knots. Of the seventeen who had leukemia in their marrow when they enrolled in the trial, fifteen witnessed the marrow become cancer-free after receiving CAR T-cells.
“These are all intensely pretreated patients who’ve gone through many previous therapies,” Turtle said. “It’s very pleasing to see patients with refractory disease react like this.”
Participants with the highest number of CAR T-cells in their blood after infusion were the most likely to have their disease vanish from bone marrow after CAR T-cell infusion. Side effects included high fevers, due to activation of CAR T-cells, and neurologic symptoms. Albeit one patient died from severe toxicity, the side effects experienced by other patients in the probe were improvised.
In a separate poster presentation from Five:30 to 7:30 p.m. on Dec. Three, the researchers will share their findings in a detailed characterization of the side effects of CD19 CAR T-cells. The poster session presentation is embargoed until nine a.m. Dec. Three – just over an hour after the embargo lifts for the CLL explore results. Turtle and his colleagues identified certain biomarkers in patients’ blood the day after infusion that were associated with the later development of the most severe toxicities. The researchers hope these biomarkers could eventually lead to tests to predict and mitigate the most serious side effects.
CAR T-cell therapy is accomplished by engineering T cells extracted from each patient’s blood. A modified virus produces genetic instructions into the cells for making a CAR, or chimeric antigen receptor, a synthetic molecule that permits T cells to recognize and kill cells bearing a particular target. In this case, the target is CD19, a molecule found on the surface of certain blood cells, including CLL cells, and the T cells are a cautiously selected, one-to-one combination of two functionally different subsets if T cells. After the CAR T-cells are grown in the lab and the patient has received chemotherapy, the fresh CAR T-cells are infused back into the patient.
CD19 CAR T-cell studies at Fred Hutch are unique because the researchers engineer specific subsets of cells from the patient and formulate the cell product to be uniform. By creating CAR T-cells with a defined composition of T cell subsets, the researchers can improve the link inbetween the dose of cells a patient receives and what they practice afterward – not just benefits, but also potential side effects.
Patients in the trial are seen at Seattle Cancer Care Alliance, Fred Hutch’s clinical care fucking partner.
Funding for this explore was provided by NCI (National Cancer Institute) R01 CA136551; NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) P30 DK56465; NCI P30 CA15704; Life Science Discovery Fund; Juno Therapeutics and philanthropists.
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek fresh and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s very first cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.