PR1 Peptide Vaccine Induces Specific Immunity With Clinical Responses In Myeloid Malignancies

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTL) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the 3 dose levels after establishing the safety of the highest dose level. Primary endpoints were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary endpoint was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8, partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders vs. 3 of 28 clinical non-responders (p=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.