PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies

• Published in: Leukemia Vol. 31; no. 3; pp. 697 - 704
• Main Authors: Qazilbash, M H, Wieder, E, Thall, P F, Wang, X, Rios, R, Lu, S, Kanodia, S, Ruisaard, K E, Giralt, S A, Estey, E H, Cortes, J, Komanduri, K V, Clise-Dwyer, K, Alatrash, G, Ma, Q, Champlin, R E, Molldrem, J J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2017; Nature Publishing Group
• Subjects: 631/250/24/590/2030; 631/92/436/108; 692/308; 692/4028/67/1990/283; 692/699/1541; 692/699/67/580; Acute myeloid leukemia; Anemia; Biomarkers; Cancer Research; Cancer therapies; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - immunology; Care and treatment; Chronic myeloid leukemia; Critical Care Medicine; Cytogenetics; Cytotoxicity; Drug dosages; Elastase; Epitopes, T-Lymphocyte - immunology; Female; Hematology; Histocompatibility antigen HLA; HLA-A2 Antigen - chemistry; HLA-A2 Antigen - immunology; Humans; Immune response; Immune system; Immunity; Immunogenicity; Immunologic Memory; Immunophenotyping; Immunotherapy; Intensive; Internal Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Leukocytes (neutrophilic); Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocytes; Lymphocytes T; Male; Medical research; Medicine; Medicine & Public Health; Myelodysplastic syndrome; Myelodysplastic syndromes; Neutrophils; Oncology; original-article; Patient outcomes; Patients; Peptides; Peptides - administration & dosage; Peptides - adverse effects; Peptides - immunology; Proteinase; Proteinase 3; Remission; Remission (Medicine); Safety; Stem cell transplantation; Survival Analysis; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Toxicity; Treatment Outcome; Vaccination; Vaccines; United States > US
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2016.254

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) 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 three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point 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 versus 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.