CD19-directed therapy using T cells genetically modified with chimeric antigen receptors (CARs) shows promise against advanced hematological malignancies, particularly as an adjuvant treatment after stem cell transplantation, according to the preliminary results of four clinical trials.
In the four ongoing clinical trials at The University of Texas MD Anderson Cancer Center, patients with B cell malignancies receive T cells modified by the novel Sleeping Beauty gene transfer system. The Sleeping Beauty system creates a CAR on the T cells that recognizes and binds to CD19, a B cell–specific protein. Thus, the CAR enables the T cells to actively target and kill CD19-expressing cancer cells.
“We are treating patients with advanced CD19-positive hematological malignancies using CAR T cells in combination with conventional blood stem cell transplantation,” said Partow Kebriaei, M.D., an associate professor in the Department of Stem Cell Transplantation and Cellular Therapy and the principal investigator of two of the clinical trials of CAR T cells. “We are also treating patients who have active disease but have not received blood stem cell transplantation.”
In the clinical trials, patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin lymphoma (NHL) receive patient- or donor-derived CAR T cells after hematopoietic stem cell transplantation or during active treatment.
Dr. Kebriaei and her colleagues reported that, of 5 NHL patients who received patient-derived CAR T cells after autologous stem cell transplantation, 4 remained in complete remission at a median of 12 months after T cell infusion. Of 10 ALL and 3 NHL patients who received donor-derived CAR T cells after allogeneic stem cell transplantation, 6 remained in complete remission at a median of 7.5 months after T cell infusion. And of the 8 ALL, 4 CLL, and 2 NHL patients with active disease who were treated with donor- or patient-derived CAR T cells, 5 showed disease regression at a median of 6 months after T cell infusion. No toxic effects from the CAR T cell treatments were observed.
Dr. Kebriaei and her colleagues presented preliminary results of the studies in December 2014 at the 56th Annual Meeting of the American Society of Hematology in San Francisco.
OncoLog, February 2015, Volume 60, Issue 2