抗独特型卵巢癌疫苗的研究

Study of anti-idiotype vaccine against ovarian carcinoma

根据免疫网络学说 ,抗独特型抗体中的Ab2 β具有模拟原始抗原的作用 ,同时也是重要的免疫调节因子。抗独特型抗体能打破免疫耐受 ,作为肿瘤疫苗具有良好的应用前景。卵巢癌相关抗原OC16 6 9在大多数上皮性卵巢癌有表达 ,我中心经过系列研究陆续制备了鼠源的模拟OC16 6 9的抗独特型抗体 6B11、6B11单链抗体(6B11scFv)、6B11scFv和人粒细胞集落刺激因子 (hGM CSF)的融合蛋白 (6B11GM)。鼠源抗体反复应用于人体可产生人抗鼠抗体 ,为了实现人源化、增加 6B11scFv的免疫原性、提高分子质量、降低鼠源性 ,我中心又制备了抗独特型微抗体 (6B11VLVHhc)。同时为了验证上述抗体的免疫作用 ,我们构建了人淋巴细胞免疫重建的荷人卵巢癌的严重联合免疫缺陷小鼠模型。上述系列研究为

In the network hypothesis of Jerne, anti-idiot ype antibody(Ab2β) can mimic th e original antigen, and also act as an important immune regulator factor. So it can overcome the immunity tolerance to be a very hopeful use as a vaccine. Ovari an cancer antigen OC166-9 is a tumor-associated antigen expressed on most ovar ia n epithelial carcinoma. We developed a murine monoclonal anti-idiotype antibody ( 6B11),6B11 single chain Fv(6B11scFv), 6B11scFv/hGM-CSF fusion protein (6B11GM). Since the antibodies were murine-derived, the clinical application is limited b e cause of human anti-mouse antibody. To realize the humanization, and improve th e imm unogenecity, we developed an anti-idiotypic minibody (6B11 V LV Hhc). We also estab lished the human PBL-SCID mouse model to invest the effect of immunotherapy of th e antibodies. The above results illustrate a very hopeful use as a vaccine for o varian carcinoma in the near future.