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    • 3. 发明申请
    • TELOMERASE REVERSE TRANSCRIPTASE FUSION PROTEIN, NUCLEOTIDES ENCODING IT, AND USES THEREOF
    • TELOMERASE逆转录酶融合蛋白,编码其的核苷酸及其用途
    • WO2008043760A1
    • 2008-04-17
    • PCT/EP2007/060713
    • 2007-10-09
    • ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI SPACILIBERTO, GennaroLA MONICA, NicolaMENNUNI, CarmelaSCARSELLI, Elisa
    • CILIBERTO, GennaroLA MONICA, NicolaMENNUNI, CarmelaSCARSELLI, Elisa
    • C07K14/435
    • C07K14/245C07K2319/00C07K2319/036C12N9/1241C12Y207/07049
    • Polynucleotides encoding telomerase reverse transcriptase (TERT) fusion proteins are provided, the TERT fusion proteins comprising a TERT protein, or functional variant thereof, fused to a substantial portion of the B subunit of heat labile enterotoxin (LTB). TERT variants useful in TERT-LTB fusion proteins of the invention comprise mutations that function to eliminate telomerase catalytic activity. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type TERT. TERT expression is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the TERT tumor-associated antigen, wherein aberrant TERT expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying polynucleotides encoding TERT fusion proteins and TERT variants and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
    • 提供了编码端粒酶逆转录酶(TERT)融合蛋白的多核苷酸,包含与热不稳定肠毒素(LTB)的B亚基的大部分融合的TERT蛋白或其功能变体的TERT融合蛋白。 在本发明的TERT-LTB融合蛋白中有用的TERT变体包含用于消除端粒酶催化活性的突变。 本发明的多核苷酸可以在哺乳动物中引发免疫应答,在优选的实施方案中,其比由野生型TERT引起的免疫应答更强。 TERT表达通常与人类癌的发展有关。 本发明提供了引发或增强对由TERT肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法,其中异常TERT表达与癌症或其发展相关。 本发明具体提供了携带编码TERT融合蛋白和TERT变体的多核苷酸的腺病毒载体和质粒构建体,并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。