Dendritic Cell Vaccine Prolongs Chemotherapy-induced AML Remission for Some Patients
NEW ORLEANS—Dendritic cell (DC) vaccination after chemotherapy-induced remission in acute myeloid leukemia (AML) has a “demonstrable” anti-relapse effect for some high-risk patients, according to results of an open-label phase 1/2 clinical trial reported at the 55th American Society of Hematology Annual Meeting and Exposition.
“Vaccination with WT1 mRNA-transfected DC is emerging as a non-toxic strategy to prevent or delay relapse in AML,” reported noted Zwi N. Berneman, MD, PhD, FRCP, and colleagues at the University of Antwerp in Edegem, Belgium. “Vaccination with dendritic cells, genetically engineered to transiently express WT1, emerges as an attractive strategy to prevent or delay relapse of AML.”
Relapse is “the major problem” in AML management, especially among older patients, most of whom cannot undergo allogeneic hematopoietic stem cell transplantation, noted Dr. Berneman. The researchers studied DC vaccination as a post-chemotherapy-remission treatment for 29 patients with AML, of whom 26 patients were in complete remission and three were in partial remission.
“DC vaccination had a demonstrable clinical antileukemic effect in eight of 29 [patients with] AML and a possible effect in another six,” the coauthors reported. “Clinical response seems to correlate with T-cell response.”
“Of these eight responding patients, three relapsed and died; five are still in complete remission, and three of them are now more than 6 years after diagnosis and most probably cured; one of those four patients was in partial remission following chemotherapy and was brought into complete and molecular remission by the DC vaccination only.”
All 15 patients who failed to normalize WT1 mRNA levels following DC vaccination relapsed “and/or died,” the authors reported.
Delayed type hypersensitivity (DTH) testing “showed immunoreactivity to the DC vaccine components in all patients tested,” they noted. “There was also evidence of natural killer cell activation following DC vaccination.”
DCs were derived from blood monocytes and electroporated with mRNA encoding the Wilms' tumor 1 protein (WT1), the authors explained. DC vaccinations were delivered intradermally. Three different WT1 constructs were used to generate mRNA by in vitro transcription, the authors reported: construct 1 encoding full-length WT1, construct 2 with a Sig-DC-LAMP major histocompatibility complex (MHC) class II-skewing signal and a deletion of the WT1 nuclear localization signal, and construct 3, a codon-optimized version of construct 2.
WT1 mRNA levels in patients' blood and marrow were monitored as a measure of minimal residual disease, Dr. Berneman reported. WT1 RNA levels are “an elegant marker to monitor molecular remission in AML patients,” he said.
“Contrary to expectations, the WT1 constructs with MHC class II-skewing signal did not seem to have superior activity over the full-length WT1 construct without that signal,” the team noted.
Dr. Berneman's discussion involved off-label use of dendritic cell vaccination.