PR1-CTL directly sort-purified from umbilical cord blood lymphocytes reduce human AML in vivo. (P4360)

Abstract

Abstract Adoptive transfer of leukemia specific CTL could prove to be a valuable tool in the prevention and/or treatment of relapse after SCT. In line with this, we chose to examine the use of PR1-specific CTL derived from UCB as a means of adoptive immunotherapy for leukemia. PR1, a 9 amino acid, HLA-A2-restricted self-peptide is well established as a dominant LAA. While cells specific for PR1 are present in the peripheral blood of healthy adults at extremely low frequencies (0.0005 to 0.05% of CD8+ T cells), we have found that the frequency of PR1-CTL in UCB is significantly higher ranging from 0.007 to 0.345% (mean 0.117%; n=57) of CD8+ cells. We hypothesized that these cells could be isolated directly from UCB via cell sorting and used in the prevention or treatment of leukemia. CD8 enriched cells were sorted and then activated ex vivo with anti-CD3/anti-CD28/IL-2. Sorted, activated cells were infused into a cohort of NSG mice with established leukemia. In three separate, but comparable, experiments the frequency of leukemia cells in the bone marrow of mice receiving PR1-specific CTL was reduced by 27% (range 21%-32%) compared to those receiving no treatment, and 23% (range 4%-47%) compared to those receiving non-specific CD8+ cells. The reduction of leukemia cells in the blood was even more pronounced with a 47% (range 45%-61%) decrease compared to the level seen in mice receiving PBS alone, and 58% (range 48%-68%) compared to mice receiving non-specific CD8+ cells.