PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies
2016; Springer Nature; Volume: 31; Issue: 3 Linguagem: Inglês
10.1038/leu.2016.254
ISSN1476-5551
AutoresM. Qazilbash, Eric Wieder, Peter F. Thall, X. Wang, R Ríos, Shan Lu, Shubham Kanodia, Kathryn Ruisaard, Sergio Giralt, Elihu H. Estey, Jorge E. Cortés, Krishna V. Komanduri, Karen Clise-Dwyer, Gheath Alatrash, Qing Ma, Richard E. Champlin, Jeffrey J. Molldrem,
Tópico(s)Acute Myeloid Leukemia Research
ResumoPR1, 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.
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