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基于分泌前列腺特异性抗原和霍乱毒素B亚基的重组鼠伤寒沙门氏菌aroA菌株的癌症免疫疗法。

Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B.

作者信息

Fensterle J, Bergmann B, Yone C L R P, Hotz C, Meyer S R, Spreng S, Goebel W, Rapp U R, Gentschev I

机构信息

Institut für Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, Wuerzburg, Germany.

出版信息

Cancer Gene Ther. 2008 Feb;15(2):85-93. doi: 10.1038/sj.cgt.7701109. Epub 2007 Dec 14.

Abstract

Prostate cancer is the most common malignant tumor in men and is normally associated with increased serum levels of prostate-specific antigen (PSA). Therefore, PSA is one potential target for a prostate cancer vaccine. In this study we analyzed the functionality of new bacterial PSA vaccines, expressed and secreted via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of Type I secretion systems (T1SS) using an attenuated Salmonella enterica serovar Typhimurium aroA strain as carrier. The data demonstrate that a bacterial live vaccine encompassing T1SS in combination with cholera toxin subunit B can be successfully used for delivery of PSA to induce cytotoxic CD8+ T-cell responses resulting in an efficient prevention of tumor growth in mice.

摘要

前列腺癌是男性最常见的恶性肿瘤,通常与血清前列腺特异性抗原(PSA)水平升高有关。因此,PSA是前列腺癌疫苗的一个潜在靶点。在本研究中,我们分析了通过大肠杆菌溶血素(HlyA)分泌系统表达和分泌的新型细菌PSA疫苗的功能,该系统是I型分泌系统(T1SS)的原型,使用减毒鼠伤寒沙门氏菌aroA菌株作为载体。数据表明,包含T1SS和霍乱毒素亚基B的细菌活疫苗可成功用于递送PSA,以诱导细胞毒性CD8+T细胞反应,从而有效预防小鼠肿瘤生长。

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