Autologous-Collected T-Cell Immunotherapy Shows Promising Antileukemia Activity in Children
(ChemotherapyAdvisor) – Using autologous T-cell immunotherapy to attack leukemia cells showed early promise in two children diagnosed with relapsing acute lymphoblastic leukemia (ALL) after bone marrow transplant, according to preliminary results from a phase 1 clinical trial, presented by National Cancer Institute (NCI) researchers at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington, DC.
“Anti-CD19 CAR (chimeric antigen receptor) T-cell therapy using patients' own immune cells is a completely new way of treating childhood cancer,” said Daniel W. Lee, MD, an assistant clinical investigator in the Pediatric Oncology Branch at the NCI in Burtonsville, MD, and coauthors. “It is not chemotherapy; therefore, it has a different side effect profile—we hope better tolerated. In the limited number of post-transplant patients we have treated so far, we're getting acceptable toxicities, and we're not seeing graft-versus-host disease.”
The vast majority of children diagnosed with ALL—more than 95%, according to Dr. Lee—achieve remission. But those that subsequently relapse face a poor prognosis.
Anti-CD19 CAR T-cell therapy using donated immune cells is under investigation for this population of patients by other research teams, but preparing donated cells is a lengthy process and time is of the essence for children with relapsed ALL, Dr. Lee said.
Seeking a faster process, the NCI researchers studied using the patient's own T cells for immunotherapy.
The phase 1 study's first three participants included one child with B-cell lymphoma and two children with ALL. Although the trial is also open to patients who had not undergone previous hematopoietic stem cell transplantation (HSCT), all three had undergone HSCT.
T cells were collected from each child and prepared in the laboratory so that they would target the leukemia cell–expressed protein CD19. The lab-modified anti-CD19 CAR T cells were then expanded in vitro for 11 days before being administered to children in the study.
“We were able to get very good expansion” in the lab, Dr. Lee noted, citing a 60-fold expansion of anti-CD19 CAR T cells in the 11-day culture period.
Early results show that although this strategy did not yield a response for the child with lymphoma, it was promising among the study's two patients with ALL, Dr. Lee said. The first patient in the trial had not achieved initial remission after being diagnosed with ALL, despite intensive chemotherapy, Dr. Lee noted.
“Strikingly, anti-CD19 CAR T-cell therapy resulted in the complete clearance of any detectable leukemia in this patient,” he said.
The other child with ALL experienced a transient complete response after autologous T-cell immunotherapy, with minimal residual disease, Dr. Lee reported. The remission's transience might have been related to that child's low T-cell count, a result of recent intensive chemotherapy, he noted.
“Altogether, these preliminary results indicate that autologous-collected anti-CD19 CAR T cell therapy in post-allogeneic HSCT patients is a reasonable and potentially effective strategy,” the researchers concluded.
The study was partly funded by the St. Baldrick's Foundation.