一种编码癌胚抗原（CEA）与粒细胞/巨噬细胞集落刺激因子（GM-CSF）基因融合体的DNA疫苗。

A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF).

作者信息

Lima Jose, Jenkins Connie, Guerrero Antonio, Triozzi Pierre L, Shaw Denise R, Strong Theresa V

机构信息

Division of Hematology and Oncology, Department of Medicine, and the Comprehensive Cancer Center, University of Alabama at Birmingham, WTI 558, 1824 6th Avenue South, Birmingham, AL 35294-3300, USA.

出版信息

Vaccine. 2005 Jan 26;23(10):1273-83. doi: 10.1016/j.vaccine.2004.08.043.

DOI:10.1016/j.vaccine.2004.08.043

PMID:15652670

Abstract

The anti-tumor immunologic effects of plasmid DNA vaccines encoding human carcinoembryonic antigen (CEA) fused to mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) were examined. Immunization of C57BL/6 mice with the CEA-GMCSF fusion plasmids in a three injection, high-dose immunization schedule led to T cell and antibody responses specific for CEA. Mice injected with CEA-GMCSF fusion plasmids also developed IgG autoantibodies to GM-CSF. Tumor challenge with the CEA-expressing syngeneic mouse adenocarcinoma line, MC38-CEA-2, showed delayed tumor growth in mice immunized with the CEA-GMCSF fusion plasmids but complete protection in mice immunized with plasmid encoding CEA alone. In contrast, a single low-dose immunization with CEA-GMCSF fusion plasmids provided better tumor protection than low-dose CEA plasmid alone and resulted in lower titers of GM-CSF antibodies.

摘要

对编码与小鼠粒细胞/巨噬细胞集落刺激因子（GM-CSF）融合的人癌胚抗原（CEA）的质粒DNA疫苗的抗肿瘤免疫效应进行了研究。采用三次注射、高剂量免疫方案，用CEA-GMCSF融合质粒免疫C57BL/6小鼠，可引发针对CEA的T细胞和抗体反应。注射CEA-GMCSF融合质粒的小鼠还产生了针对GM-CSF的IgG自身抗体。用表达CEA的同基因小鼠腺癌系MC38-CEA-2进行肿瘤攻击，结果显示，用CEA-GMCSF融合质粒免疫的小鼠肿瘤生长延迟，而单独用编码CEA的质粒免疫的小鼠则得到完全保护。相比之下，用CEA-GMCSF融合质粒进行单次低剂量免疫比单独使用低剂量CEA质粒能提供更好的肿瘤保护，且产生的GM-CSF抗体滴度更低。