第一情报 ---生物与医药

肿瘤免疫疫苗-人绒毛膜促性腺激素疫苗

供稿人:彭建新  供稿时间:2004-12-1   关键字:肿瘤  免疫  疫苗  人绒毛膜促性腺激素  hCG  hCGβ  
    近来发现,几乎全部的恶性肿瘤细胞均能表达异位人绒毛膜促性腺激素(hCG),分泌型异位hCG具有生长因子功能,与恶性肿瘤自我生长的调控有关;而膜结合型hCG(特别是富含负电荷糖链的自由hCGβ链及其片段)与恶性肿瘤转移特性、恶性化程度以及肿瘤微环境和免疫耐受的形成等有一定的关系。
 
    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, hypertension, diabetes and associated 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 response to human chorionic gonadotropin (hCG), useful for treatment of cancer and fertility control comprises exposing cells to nucleic acid construct encoding hCG immunogenic epitope
UNIV OHIO STATE
US6096318
New antigen for treating hormone related diseases, is conjugated with a specific polypeptide which elicits an antibody response against 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 against 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 groups
UNIV OHIO STATE
US6146633
Immunizing selected mammalian species 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 gonadotropin, contains a peptide comprising disulfide bridges linking terminal cysteine residues to form a loop
VICAL INC
WO200109303
Immunogenic compositions comprising Flt-3 ligand encoding polynucleotide and one or more antigen, or cytokine encoding polynucleotides, useful for suppressing tumor growth and for treating autoimmune diseases (e.g. rheumatoid arthritis)
METATRON INC
US6331610
New peptide derived from the beta subunit of human chorionic gonadotropin or their peptide fragment, are useful in the treatment of human immunodeficiency virus in human cells
PHARMEXA AS
WO200234287
Inducing or enhancing an immune response against an antigen, particularly cytotoxic T-lymphocyte responses, for treating or ameliorating prostate or breast cancer, comprises administering the antigen formulated with chitosan
ACEVEDO H F
KAMICA CO
WO200285311
Pharmaceutical formulation useful for treating e.g. HIV, cancer, AIDS, Kaposi's sarcoma, multiple myeloma, lymphoma and melanoma, comprising human chorionic gonadotropin dimer and muramyl peptide
UNIV COLORADO STATE RES FOUND
US2002165126
Method for sterilizing a mammal involves use of compound containing peptide hormone conjugated to plant or bacterial toxins having toxin domain and a translocation domain
UNIV TEXAS SYSTEM
PAUL S NISHIYAMA Y
WO200279223-
Novel covalently reactive transition state antigen analog useful for stimulating production of catalytic antibodies, and actively immunizing patient against particular pathogen to generate protective immunity
UNIV MARYLAND BIOTECHNOLOGY INST
US6699834
Treating and inhibiting the growth of cancer, HIV infections and wasting syndrome in a subject by administering a protein or peptide having at least one segment of the beta-human chorionic gonadotropin
FABRE MEDICAMENT SA PIERRE
WO2003095486
New peptides from human chorionic gonadotropin, useful for treatment or prevention of cancer, induce a cytotoxic T cell response
UNIV MARYLAND BIOTECHNOLOGY INST
US6620416
Treating HIV infection in a subject comprises administering to the subject an isolated protein or peptide comprising at least one amino acid segment selected from a 5-50 amino acids of beta-human chorionic gonadotropin (hCG)
MEDAREX INC
WO2004074432
MILKHAUS LAB INC
US2004072731
Treatment of chronic pelvic pain syndrome, e.g. chronic prostatitis, comprises administering chorionic gonadotropin or its fragment or derivative
MILKHAUS LAB INC
US2004072731
Treatment of chronic pelvic pain syndrome, e.g. chronic prostatitis, comprises administering chorionic gonadotropin or its fragment or derivative
申庆祥
CN1361181-A
上海市计划生育科学研究所;复旦大学
CN1438242
人绒毛膜促性腺激素生物合成嵌合肽及其制备方法
复旦大学;上海市计划生育科学研究所
CN1446825
人绒毛膜促性腺激素基因工程合成嵌合肽及其制备方法

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