ASH 2015: Engineered Donor T Cells May Eradicate Progressive Disease After Stem Cell Transplant
A study (Abstract 99) to be reported today by Brudno et al at the 57th American Society of Hematology (ASH) Annual Meeting was the first clinical trial to use engineered donor immune cells to prevent progressive cancer after stem cell transplantation. The findings were presented at a press conference during the ASH meeting.
Progressive disease is a leading cause of death after stem cell transplant. If a patient’s cancer continues to spread after transplant, the current standard treatment is to infuse the patient with unmanipulated donor white blood cells to fight the disease. However, this procedure is often ineffective and increases the risk of graft-vs-host disease.
Researchers hypothesized that instead of using unmanipulated white blood cells, an infusion of genetically engineered donor T cells would eradicate progressive disease after stem cell transplant in patients with B-cell malignancies.
Study Details
Researchers conducted a clinical trial in which donor T cells were engineered to express a chimeric antigen receptor (CAR). CAR T cells are programmed to first recognize CD19, a protein on the surface of most B cells, and then attack the targeted cell.
Patients who experienced resurgence of B-cell malignancies after stem cell transplant received a single infusion of CAR T cells obtained from each recipient’s stem cell donor. No chemotherapy or other therapies were administered.
Of 20 patients receiving the treatment, 8 obtained remissions, including 6 complete remissions and 2 partial remissions. Response rates were highest for patients with acute lymphocytic leukemia, with four of five patients achieving complete remission. The longest ongoing complete remission is more than 30 months in a patient with chronic lymphocytic leukemia.
No patient developed graft-vs-host disease after infusion with CAR T cells.
The findings support the hypothesis that infusing anti-CD19 donor CAR T cells is a promising method for treating B-cell malignancies that emerge after stem cell transplant. The investigators concluded: “Our findings point toward a future in which antigen-specific T-cell therapies will be an important part of the field of allogeneic hematopoietic stem cell transplantation.”
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