An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice.
An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice.
复制标题
针对人类癌胚抗原 (CEA) 的口服 DNA 疫苗可预防 CEA 转基因小鼠中 Lewis 肺癌的生长和扩散。
DOI：
10.1016/s0264-410x(01)00362-0
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发表时间：
2001
期刊：
影响因子：
5.5
通讯作者：
Reisfeld,RA
中科院分区：
文献类型：
--
作者：
Niethammer,AG;Primus,FJ;Xiang,R;Dolman,CS;Ruehlmann,JM;Ba,Y;Gillies,SD;Reisfeld,RA
编码人癌胚抗原（CEA）的DNA疫苗打破了CEA转基因C57 BL/6 J小鼠中外周T细胞对由CEA稳定转导的刘易斯肺癌表达的这种肿瘤自身抗原的耐受。该疫苗，通过口服管饲法与减毒株鼠伤寒沙门氏菌（SL 7207），并加强与抗体-IL 2融合蛋白，诱导肿瘤保护性免疫介导的MHC I类抗原限制性CD 8 +T细胞，导致根除皮下肿瘤的100%的小鼠和预防实验性肺转移的75%的实验动物。CTL和抗原呈递树突状细胞都被激活，如其各自的激活标志物CD 2、CD 25、CD 28以及CD 48和CD 80的决定性增加所示。在预防性环境中获得的这种基于CEA的DNA疫苗的抗肿瘤作用表明，这种方法可以导致合理设计有效的人类肺癌治疗方式。
A DNA vaccine encoding human carcinoembryonic antigen (CEA) broke peripheral T-cell tolerance toward this tumor self-antigen expressed by Lewis lung carcinoma stably transduced with CEA in C57BL/6J mice transgenic for CEA. This vaccine, delivered by oral gavage with an attenuated strain of Salmonella typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, induced tumor-protective immunity mediated by MHC class I antigen-restricted CD8+T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experimental animals. Both CTL and antigen-presenting dendritic cells were activated as indicated by a decisive increase in their respective activation markers CD2, CD25, CD28 as well as CD48 and CD80. The antitumor effects of this CEA-based DNA vaccine obtained in prophylactic settings, suggest that this approach could lead to the rational design of effective treatment modalities for human lung cancer.