根据我们实验室的报告,针对WT1的癌症疫苗疗法也显示出了令人鼓舞的结果,2009年美国国家癌症研究所的75种癌症抗原来自海外,1)治疗效果,2)免疫原性,3)特异性,4)致癌性,5)表达水平和阳性率,6)在癌干细胞中表达,7)抗原阳性患者数量,8)表位数量,9)抗原表达位点WT1蛋白在9个项目的评分排名中,WT 1蛋白在“期待的癌症抗原排行榜”中排名第一(Cheever et al.Clin Cancer Res 2009)。
1、HLA class I-restricted peptides are injected intradermally or subcutaneously along with some immune adjuvant.Peptides bind to the HLA class I molecules on the surface of DCs,or are taken up and presented on the cell surface along with HLA class I molecules by immature DCs.Immune adjuvant injected at the same time stimulates immature DCsin peripheral tissues。
2、These activated DCsmigrate via lymphatics to regional lymph nodes,where they arrive as fully mature DCsthat express both antigen/HLA-molecule complexes and costimulatory molecules necessary to stimulate antigen-specifi c T-lymphocytes.
3、Antigen-specifi c T-lymphocytes,especially CD8+cytotoxic T-lymphocytes(CTLs),are stimulated to proliferate and differentiate by mature DCsand form a clone of effecter cells.
4、Ultimately,antigen-specifi c CTL senter the tumor bed,and kill the targeted cancer cells by inducing apoptosis and releasing specialized cytotoxic granules,such as perforin and granzymes,upon recognition of the antigen on the surfaces of tumor cells.