Chen C H, Wang T L, Hung C F, Pardoll D M, Wu T C
Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, USA.
Vaccine. 2000 Apr 3;18(19):2015-22. doi: 10.1016/s0264-410x(99)00528-9.
We have previously linked the sorting signals of the lysosome-associated membrane protein-1 (LAMP-1) to HPV-16 E7 antigen, creating a chimera, Sig/E7/LAMP-1. We found that both Sig/E7/LAMP-1-containing recombinant vaccinia virus (Vac-Sig/E7/LAMP-1) and Sig/E7/LAMP-1 DNA can generate strong antitumor immunity. To determine whether combination of Sig/E7/LAMP-1 DNA and Vac-Sig/E7/LAMP-1 can further enhance immune responses, sequential vaccination with Sig/E7/LAMP-1 DNA and Vac-Sig/E7/LAMP-1 was given. We found that priming with Sig/E7/LAMP-1 DNA and boosting with Vac-Sig/E7/LAMP-1 generated the strongest E7-specific CD8(+) T cell responses. Our results encourage the use of the DNA prime/vaccinia booster regimen in future clinical trials.
我们之前已将溶酶体相关膜蛋白-1(LAMP-1)的分选信号与HPV-16 E7抗原相连,构建了一种嵌合体,即Sig/E7/LAMP-1。我们发现,含Sig/E7/LAMP-1的重组痘苗病毒(Vac-Sig/E7/LAMP-1)和Sig/E7/LAMP-1 DNA均可产生强大的抗肿瘤免疫力。为了确定Sig/E7/LAMP-1 DNA与Vac-Sig/E7/LAMP-1联合使用是否能进一步增强免疫反应,我们先后接种了Sig/E7/LAMP-1 DNA和Vac-Sig/E7/LAMP-1。我们发现,先用Sig/E7/LAMP-1 DNA进行初次免疫,再用Vac-Sig/E7/LAMP-1进行加强免疫,可产生最强的E7特异性CD8(+) T细胞反应。我们的结果鼓励在未来的临床试验中使用DNA初免/痘苗加强免疫方案。