PR1 vaccination in myeloid malignancies

Abstract

The graft-versus-leukemia (GVL) effect following allogeneic stem cell transplantation is testament to the effectiveness of the immune system in recognizing and eliminating leukemia cells. The successful identification of a range of leukemia-associated antigens (LAAs) that drive the GVL response in recent years has stimulated research in the development of vaccines to treat hematological malignancies. Here, we review the current experience with the PR1 vaccine. PR1 is a nine amino acid, HLA-A*0201-restricted peptide, shared by two myeloid LAAs, proteinase (PR)3 and neutrophil elastase (NE). PR3 and NE are found in the primary (azurophil) granule proteins of normal granulocytes and are overexpressed in myeloid leukemia cells. PR1 induces powerful HLA-A*0201-restricted CD8+ T-cell responses that selectively kill myeloid leukemia cells in vitro. The detection of low frequencies of PR1-specific CD8+ T cells in patients with chronic myeloid leukemia and at higher frequencies in patients entering molecular remission after allogeneic stem cell transplantation supports the concept that there is natural immunity to PR1, which can be boosted further by vaccination to enhance immunity to leukemia. Preliminary reports indicate that PR1 peptide vaccination induces significant increases in PR1-specific CD8+ T cells, with rapid and durable remissions in some patients with myeloid leukemia. These promising early results point the way to optimizing the administration of peptide vaccines to improve the treatment of otherwise refractory myeloid leukemias.