Schmitt Michael, Casalegno-Garduño Rosaely, Xu Xun, Schmitt Anita
Head of Clinical Stem Cell Transplantation and Cellular Therapy, Department of Internal Medicine III, University of Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany.
Expert Rev Vaccines. 2009 Oct;8(10):1415-25. doi: 10.1586/erv.09.90.
The majority of patients with acute myeloid leukemia (AML) under 60 years of age reach a complete hematological remission after intensive chemotherapy. However, only 20-40% of all patients with AML achieve a disease-free survival of more than 5 years. The graft-versus-leukemia effect observed after allogeneic stem cell transplantation and donor lymphocyte infusions strongly suggests that T lymphocytes play a major role in the rejection of leukemic cells. Vaccination with leukemia-associated antigen (LAA) peptides might constitute a way to augment the graft-versus-leukemia effect. Peptide vaccination causes no major side effects, which is of particular note as most AML patients are people over 60 years of age, often suffering from concomitant disease. This review summarizes approaches to define appropriate LAAs as targets of a T-cell-based vaccine immunotherapy. Current clinical LAA peptide vaccination protocols targeting Wilms' tumor gene, proteinase-3 and the receptor for hyaluronan-mediated motility are reviewed and an outlook to dendritic cells, adjuvants and short oligodenucleotides is given.
大多数60岁以下的急性髓系白血病(AML)患者在接受强化化疗后可实现完全血液学缓解。然而,所有AML患者中只有20%-40%能实现5年以上的无病生存。异基因干细胞移植和供体淋巴细胞输注后观察到的移植物抗白血病效应强烈表明,T淋巴细胞在白血病细胞的排斥中起主要作用。用白血病相关抗原(LAA)肽进行疫苗接种可能是增强移植物抗白血病效应的一种方法。肽疫苗接种不会引起重大副作用,这一点尤其值得注意,因为大多数AML患者是60岁以上的人群,常伴有其他疾病。本综述总结了将合适的LAA定义为基于T细胞的疫苗免疫疗法靶点的方法。综述了目前针对威尔姆斯瘤基因、蛋白酶-3和透明质酸介导的运动受体的临床LAA肽疫苗接种方案,并对树突状细胞、佐剂和短寡脱氧核苷酸进行了展望。