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首页> 外文期刊>Human gene therapy. Clinical development >Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer Vaccine Targeting Carcinoembryonic Human Antigen
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Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer Vaccine Targeting Carcinoembryonic Human Antigen

机译：靶向癌胚人类抗原的异种遗传癌症疫苗的优越的免疫学和治疗功效。

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摘要

We have generated a xenogeneic vaccine against human carcinoembryonic antigen (hCEACAM-5 or commonly hCEA) using as immunogen rhesus CEA (rhCEA). RhCEA cDNA was codon-usage optimized (rhCEAopt) and delivered by sequential DNA electro-gene-transfer (DNA-EGT) and adenoviral (Ad) vector. RhCEAopt was capable to break tolerance to CEA in hCEA transgenic mice and immune responses were detected against epitopes distributed over the entire length of the protein. Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells. The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected. Our data show that xenogeneic gene-based vaccination with rhCEA is a viable approach to break tolerance against CEA, thus suggesting further development in the clinical setting.
机译：我们已经使用恒河猴CEA（rhCEA）作为免疫原，生成了针对人类癌胚抗原（hCEACAM-5或通常为hCEA）的异种疫苗。 RhCEA cDNA经过密码子使用优化（rhCEAopt），并通过顺序DNA电基因转移（DNA-EGT）和腺病毒（Ad）载体递送。 RhCEAopt能够打破hCEA转基因小鼠对CEA的耐受性，并检测到针对分布在蛋白质全长上的抗原决定簇的免疫反应。除自身反应性CD8 + T细胞外，rhCEA的异种疫苗接种还导致CD4 + T细胞反应的激活，针对hCEA的高滴度抗体的开发以及对hCEA +肿瘤细胞攻击后的显着抗肿瘤作用。在hCEA / HHD双转基因小鼠中证实了rhCEAopt优于hCEAopt的活性，其中检测到针对特定人HLA A * 0201 hCEA表位的有效CD8 + T细胞应答。我们的数据表明，rhCEA基于异种基因的疫苗接种是打破对CEA的耐受性的可行方法，因此表明在临床环境中的进一步发展。

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