A clinical trial at The University of Texas MD Anderson Cancer Center involving CD19-directed chimeric antigen receptor (CAR) therapy that modifies T-cells using Sleeping Beauty non-viral transduction continues to show promise in treating patients with advanced hematologic malignancies. New results from the study–which looks at patients with acute lymphocytic leukemia (ALL), non-Hodgkin lymphoma (NHL), or chronic lymphocytic leukemia (CLL)–were presented at the 56th Annual Meeting of the American Society of Hematology (ASH) annual conference and published in the ASH journal Blood.
“We are treating patients with advanced CD19 positive hematologic malignancies using CAR T-cells in combination with conventional blood stem cell transplantation,” explained Partow Kebriaei, MD, who worked with Laurence Cooper, MD, PhD, to use the Sleeping Beauty gene transfer system for the trial. “We are also treating patients who had active disease but had not received blood stem cell transplantation.”
The clinical trial has gained a lot of ground since the last time the Sleeping Beauty CAR T-cell therapy was discussed at ASH. “Five patients at high risk for relapse were treated with CAR T-cells along with autologous stem cell transplant, and four of those patients remain in complete remission with a median follow-up of 12 months,” said Dr. Kebriaei. “Among 13 patients treated with donor CAR T-cells after allogeneic stem cell trasnsplantation, six remain in complete remission with a median follow-up of 7.5 months.”
For five out of 14 patients with active disease who were not treated with blood stem cell transplantation, signs of disease regression were present at a median follow-up of six months. Of the 33 patients treated so far, none has experienced acute or long-term toxicity.
Sleeping Beauty acts to modify T-cells by awakening an extinct transposon, allowing gene transfer of DNA into a plasmid. Through funding by the National Institute of Health and the Cancer Prevention and Research Institute of Texas, scientists at MD Anderson’s Moon Shots program are further developing this approach to lead to future clinical treatments for cancer.