Hutchings Yalonda, Osada Takuya, Woo Christopher Y, Clay Timothy M, Lyerly H Kim, Morse Michael A
Duke University Medical Center, Departments of Medicine and Surgery, 401 MSRB, Research Drive, Durham, NC 27710, USA.
Curr Opin Mol Ther. 2007 Feb;9(1):62-9.
The expression of Wilms' tumor protein (WT1)-derived peptides on malignant cell surfaces and recognition of those peptides by cellular and humoral immune responses suggest that WT1 may be a promising potential target antigen in immunotherapeutic trials. With a high frequency of expression in hematopoietic as well as solid tumors, WT1 is a broadly applicable target. Both in vivo mouse model and in vitro human studies have demonstrated the ability of WT1-specific cytotoxic T-lymphocytes to lyse WT1-expressing malignancies without harming normal tissue. WT1-peptide vaccination, in combination with adjuvants, has demonstrated the ability to activate WT1-specific immune responses and evidence of clinical activity. Because peptide-based vaccines are human leukocyte antigen-restricted, other more broadly applicable strategies are now being developed to activate WT1-specific immune responses, including the use of WT1-specific viral vectors.
肾母细胞瘤蛋白（WT1）衍生肽在恶性细胞表面的表达以及细胞免疫和体液免疫反应对这些肽的识别表明，WT1可能是免疫治疗试验中一个很有前景的潜在靶抗原。WT1在造血系统肿瘤和实体瘤中均有高频率表达，是一个广泛适用的靶点。体内小鼠模型和体外人体研究均已证明，WT1特异性细胞毒性T淋巴细胞能够裂解表达WT1的恶性肿瘤细胞，而不损害正常组织。WT1肽疫苗与佐剂联合使用，已证明能够激活WT1特异性免疫反应并有临床活性证据。由于基于肽的疫苗受人类白细胞抗原限制，目前正在开发其他更广泛适用的策略来激活WT1特异性免疫反应，包括使用WT1特异性病毒载体。
