An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells
An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells
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一种腺病毒载体癌症疫苗，可将肿瘤相关抗原/CD40配体融合蛋白传递至树突状细胞
DOI：
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发表时间：
2003
影响因子：
11.1
通讯作者：
A. Deisseroth
中科院分区：
文献类型：
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作者：
Lixin Zhang;Yucheng Tang;H. Akbulut;D. Zelterman;P. Linton;A. Deisseroth
为了开发一种克服肿瘤宿主对癌症无反应性的方法，我们设计了一种腺病毒载体，用于体内激活和负载树突状细胞的肿瘤抗原。该腺病毒载体编码由融合至CD 40配体（CD 40 L）的氨基末端肿瘤相关抗原片段组成的融合蛋白。皮下注射编码人乳头瘤病毒E7外源抗原与CD 40 L连接的融合蛋白的腺病毒载体在C57 BL/6小鼠中产生对E7阳性同基因TC-1癌细胞生长的CD 8 + T细胞依赖性免疫抗性长达1年。我们还研究了s.c.注射携带与CD 40 L融合的人MUC-1（hMUC-1）自身抗原的基因的载体。当将该载体注射到hMUC-1抗原转基因的hMUC-1.Tg小鼠中时，同基因hMUC-1阳性LL 1/LL 2 hMUC-1小鼠癌细胞的生长在100%的注射动物中被抑制。在注射载体之前，hMUC-1.Tg小鼠对hMUC-1抗原无反应性。这些实验结果表明，有可能使用载体注射来激活无反应性动物中针对自身抗原的持久细胞免疫应答。树突状细胞的载体介导的体内活化和肿瘤相关抗原加载不需要额外的细胞因子加强来诱导针对肿瘤细胞的免疫应答。因此，这种载体策略可用于开发hMUC-1抗原过表达的许多癌的免疫疗法。
To develop a method to overcome the anergy that exists in tumor hosts to cancer, we have designed an adenoviral vector for the in vivo activation and tumor antigen loading of dendritic cells. This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L). Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year. We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L. When this vector was injected into hMUC-1.Tg mice, which are transgenic for the hMUC-1 antigen, the growth of syngeneic hMUC-1-positive LL1/LL2hMUC-1 mouse cancer cells was suppressed in 100% of the injected animals. The hMUC-1.Tg mice are anergic to the hMUC-1 antigen before the injection of the vector. These experimental results show that it is possible to use vector injection to activate a long-lasting cellular immune response against self-antigens in anergic animals. The vector-mediated in vivo activation, and tumor-associated antigen loading of dendritic cells does not require additional cytokine boosting to induce the immune response against the tumor cells. This vector strategy may therefore be of use in the development of immunotherapy for the many carcinomas in which the hMUC-1 antigen is overexpressed.
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影响因子：
11.2
作者：
Antoni Ribas;Lisa H. Butterfield;S. Amarnani;V. Dissette;Donald Kim;Wilson S. Meng;Gustavo A. Miranda;H. Wang;William H. McBride;John A. Glaspy;J. Economou
通讯作者：
Antoni Ribas;Lisa H. Butterfield;S. Amarnani;V. Dissette;Donald Kim;Wilson S. Meng;Gustavo A. Miranda;H. Wang;William H. McBride;John A. Glaspy;J. Economou
用肿瘤抗原 MUC1 粘蛋白串联重复肽对黑猩猩进行免疫接种，可引发辅助 T 细胞反应和细胞毒性 T 细胞反应。
DOI：
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发表时间：
1999
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research.
影响因子：
--
作者：
Barratt-Boyes,SM;Vlad,A;Finn,OJ
通讯作者：
Finn,OJ
影响因子：
20.3
作者：
Toshiaki Kikuchi;Malcolm A. S. Moore;Ronald G. Crystal
通讯作者：
Toshiaki Kikuchi;Malcolm A. S. Moore;Ronald G. Crystal
CD4淋巴细胞在体内提供MUC1特异性肿瘤免疫，这种免疫在体外无法检测到，并且在MUC1转基因小鼠中不存在。
DOI：
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发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Tempero,RM;VanLith,ML;Morikane,K;Rowse,GJ;Gendler,SJ;Hollingsworth,MA
通讯作者：
Hollingsworth,MA
影响因子：
5.7
作者：
KARPUSAS, M;HSU, YM;THOMAS, D
通讯作者：
THOMAS, D