许多实验证明，由hCGβ、重组蛋白，hCGβ片段及其表达载体制作的疫苗，能够激发体内产生有效的免疫反应，具有抑制肿瘤细胞生长的作用。美国Medarex公司将肿瘤相关抗原hCGβ连接到人抗-DC抗体(B11)，获得融合蛋白B11-hCGβ；对融合蛋白B11-hCGβ在体外激发人肿瘤抗原特异性细胞免疫反应的能力检测发现，DCs能促进B11-hCGβ对肿瘤抗原的吸收和加工，产生肿瘤特异性的HLAI和HLAII-类限制性T-细胞反应，包括能杀死表达hCGβ的人癌细胞系的CTLs发应Clin （Cancer Res.2004,10(6):1920-7）。英国伦敦大学学院检测了表达hCGβ及其融合蛋白DNA疫苗的免疫效应，发现表达膜结合型和分泌型hCGβ的DNA疫苗均可产生中等水平的抗体响应；表达hCGβ-hFc融合蛋白的质粒不能提高免疫动物的抗体水平；用表达hCGβ-C3d3融合蛋白的质粒免疫小鼠产生的抗体水平低于hCGβ的DNA疫苗（Vaccine.2004,22(17-18):2146-53）。中国科学院动物研究所和计划生育生殖生物学国家重点实验室构建了PCR3.1-hCGβDNA 疫苗, 其能够在HeLa细胞中高效表达hCGβ蛋白, 表达的hCGβ蛋白主要存在于细胞内。将20μg PCR3.1-hCGβ质粒DNA 通过普鲁卡因盐酸盐(bupivacaine-HCl) 药物诱导后接种小鼠肌肉, 小鼠能够吸收质粒DNA , 并表达编码的hCGβ蛋白抗原, 表达的hCGβ被小鼠的免疫系统识别, 同时激发hCGβ抗原特异性的体液免疫和细胞免疫反应, 抗体滴度最高可超过1∶8000 , 并且这两种类型的免疫应答均能够在体外作用于HeLa细胞, 诱导其发生细胞凋亡, 表明PCR3.1-hCGβDNA 疫苗激发的免疫反应在体外具有抗肿瘤作用。
异位hCG与恶性肿瘤发生、发展的关系日益受到人们关注,以异位hCG为靶抗原的肿瘤疫苗也成为肿瘤生物治疗新的研究热点。下表介绍2000年至今有关hCG或其片段应用于肿瘤治疗的专利申请。
申请人 公开号 题目
UNIV OHIO US6039948 Antigenically modified polypeptides useful for treating cancer, hyperte ion, diabetes and a ociated vascular diseases comprises immunogenic polypeptides conjugated to carrier moieties
FOX CHASE CANCER CENT EP1013281 Treating mammary tumors in pre- and post-menopausal women by administering human chorionic gonadotropin, Type I interferon and an antiestrogen such as Tamoxifen
AVI BIOPHARMA INC
IVERSEN P L WO200041717- Inducing immune re o e to human chorionic gonadotropin (hCG), useful for treatment of cancer and fertility control comprises exposing cells to nucleic acid co truct encoding hCG immunogenic epitope
UNIV OHIO STATE US6096318 New antigen for treating hormone related diseases, is conjugated with a ecific polypeptide which elicits an antibody re o e agai t human chorionic gonadotropin
UNIV WASHINGTON US6103501 Single chain glycoprotein hormones comprising two beta and one alpha subunits and recombinant production thereof
UNIV OHIO STATE US6143305 Antigenically modified polypeptide composition used as a vaccine agai t human chorionic gonadotropin
AVI BIOPHARMA INC WO200069915 Human, anti-human chorionic gonadotropin (hCG) monoclonal antibody immunoreactive with a 21mer N-terminal fragment of C-terminal 37 subunits of hCG beta subunit, used to treat cancer along with vaccine comprising hCG grou
UNIV OHIO STATE US6146633 Immunizing selected mammalian ecies with antigenically modified peptides for the production of polyclonal antibodies for contraception, abortion or treatment of hormone-related disease states such as cancer
UNIV WASHINGTON US6242580 Single-chain forms of the glycoprotein hormone quartet
UNIV WASHINGTON US6238890 Single chain forms of the glycoprotein hormone quartet
UNIV OHIO STATE RES FOUND US6217881 Novel vaccine composition for provoking the formation of antibodies to human chorionic g