WT1 plus 肿瘤疫苗原理是什么

Principle of WT1 Peptide-Based  Cancer Vaccine
基于肽的WT1 癌症疫苗原理
In most of cancer immunotherapy , the key process involves exploiting the intrinsic capacity of dendritic cells ( DCs )in vivo or ex vivo in order to induce antigen-specifi c T-cell responses . Peptidebased cancer vaccines, which are simple and easily adapted to a variety of cancer patients, are widely used in clinical trials . The principles of peptide-based cancer vaccines, which consist of HLA class I-restricted peptide and immune adjuvant, are as follows (Fig. 1)
在大多数癌症免疫疗法中，关键过程涉及在体内或离体利用树突细胞（DC）的内在能力以诱导抗原特异性T细胞应答。 基于肽的癌症疫苗简单且易于适应各种癌症患者，广泛用于临床试验。 基于肽的癌症疫苗的原理，其由HLA I类限制性组成肽和免疫佐剂如下（图1）。

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。
HLA I类限制性肽与一些免疫佐剂一起皮内或皮下注射。 肽与DC表面上的HLA I类分子结合，或被未成熟DC吸收并与HLA I类分子一起呈递在细胞表面上。 同时注射的免疫佐剂刺激未成熟的DCsin外周组织


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 .
这些活化的DC通过淋巴管转移至区域淋巴结，在那里它们作为完全成熟的DC到达，其表达抗原/ HLA-分子复合物和刺激抗原特异性T-淋巴细胞所必需的共刺激分子。


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.
抗原特异性T淋巴细胞，尤其是CD8 +细胞毒性T淋巴细胞（CTL）被成熟DC刺激增殖和分化，并形成有效细胞的克隆。


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.
最终，抗原特异性CTL引发肿瘤床，并且在识别肿瘤细胞表面上的抗原后，通过诱导细胞凋亡并释放特异性细胞毒性颗粒（例如穿孔素和颗粒酶）来杀死靶向癌细胞。