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
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Adult Stem Cell Transplant Program and Department of Medicine, University of Miami Sylvester Cancer Center, Miami, FL, USA.
Leukemia. 2017 Mar;31(3):697-704. doi: 10.1038/leu.2016.254. Epub 2016 Sep 22.
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.
PR1是一种源自蛋白酶3和中性粒细胞弹性蛋白酶的HLA - A2限制性肽，在髓系白血病细胞上被细胞毒性T淋巴细胞（CTL）识别，这些CTL优先杀伤白血病细胞并有助于细胞遗传学缓解。为了评估PR1疫苗接种的安全性、免疫原性和临床活性，开展了一项I/II期试验。66例HLA - A2阳性的急性髓系白血病（AML：42例）、慢性髓系白血病（CML：13例）或骨髓增生异常综合征（MDS：11例）患者接受了三至六次PR1肽疫苗接种，每3周皮下注射一次，剂量水平为0.25、0.5或1.0毫克。在确定最高剂量水平的安全性后，患者被随机分配到三个剂量组。主要终点是安全性和免疫反应，通过PR1/HLA - A2四聚体特异性CTL数量翻倍来评估，次要终点是临床反应。66例患者中有35例（53%）出现免疫反应。在53例可评估的活动性疾病患者中，12例（24%）有客观临床反应（完全缓解：8例；部分缓解：1例；血液学改善：3例）。25例临床反应者中有9例出现PR1特异性免疫反应，而28例临床无反应者中有3例出现（P = 0.03）。总之，PR1肽疫苗可诱导特异性免疫，这与AML、CML和MDS患者的临床反应相关，包括分子缓解。
