Hallermalm K, Johansson S, Bråve A, Ek M, Engström G, Boberg A, Gudmundsdotter L, Blomberg P, Mellstedt H, Stout R, Liu M A, Wahren B
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Scand J Immunol. 2007 Jul;66(1):43-51. doi: 10.1111/j.1365-3083.2007.01945.x.
In preparation for a clinical trial in patients diagnosed with colorectal cancer, a vaccination strategy targeting the carcinoembryonic antigen (CEA) was evaluated in mice using a GMP-produced plasmid DNA vaccine, CEA66, encoding a truncated form of the tumour-associated antigen, CEA. The GMP-produced CEA DNA vaccine was also evaluated for toxicity. Repeated intradermal administration of the GMP-produced vaccine using a novel needle-free jet injection device (Biojector) induced robust CD4 and CD8 T-cell responses in mice, and did not result in any vaccine-related toxicity. In a heterologous DNA prime/protein boost setting, cellular immune responses were of higher magnitude in animals primed with CEA66 DNA than in animals receiving repeated doses of recombinant CEA protein. These responses were further enhanced if recombinant murine granulocyte-macrophage colony-stimulating factor was given as an adjuvant prior to vaccination. In contrast to repeated administration of recombinant CEA protein as a single modality vaccine, the heterologous CEA66 DNA prime/rCEA boost vaccination strategy resulted in a qualitatively broader immune response, and supports clinical testing of this vaccination regimen in humans.
在为诊断患有结直肠癌的患者准备一项临床试验时，使用一种由GMP生产的编码肿瘤相关抗原癌胚抗原（CEA）截短形式的质粒DNA疫苗CEA66，在小鼠中评估了一种针对癌胚抗原（CEA）的疫苗接种策略。还评估了由GMP生产的CEA DNA疫苗的毒性。使用新型无针喷射注射装置（Biojector）对由GMP生产的疫苗进行反复皮内给药，可在小鼠中诱导强烈的CD4和CD8 T细胞反应，且未导致任何与疫苗相关的毒性。在异源DNA初免/蛋白加强免疫方案中，用CEA66 DNA初免的动物的细胞免疫反应比接受反复剂量重组CEA蛋白的动物更强。如果在接种疫苗前给予重组鼠粒细胞巨噬细胞集落刺激因子作为佐剂，这些反应会进一步增强。与将重组CEA蛋白作为单一模式疫苗反复给药相比，异源CEA66 DNA初免/rCEA加强免疫接种策略产生了质量上更广泛的免疫反应，并支持在人类中对该疫苗接种方案进行临床试验。
