Immunity to Trop-1, a newly identified breast cancer antigen, inhibits the growth of breast cancer in mice.
Immunity to Trop-1, a newly identified breast cancer antigen, inhibits the growth of breast cancer in mice.
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DOI：
10.1016/j.vaccine.2010.09.057
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发表时间：
2010-11
期刊：
影响因子：
5.5
通讯作者：
Byeong C Lee;M. Jung;D. Cho;I. O-Sullivan;E. Cohen;T. S. Kim
中科院分区：
文献类型：
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作者：
Byeong C Lee;M. Jung;D. Cho;I. O-Sullivan;E. Cohen;T. S. Kim
本研究描述了编码肿瘤相关钙信号转导蛋白-1(trop-1)的疫苗在乳腺癌小鼠中的免疫治疗特性。此前，我们发现，与未强化的疫苗相比，trop-1在细胞乳腺癌疫苗中过度表达，与未强化的疫苗相比，这些疫苗高度浓缩了诱导乳腺癌小鼠治疗性CTL中介免疫反应的细胞。在这项研究中，为了确定强化疫苗中细胞表达trop-1是否与其治疗效果有关，我们将一种特定于trop-1基因的表达载体导入LM成纤维细胞，并将其用作疫苗。为了增强其免疫原性，在trop-1DNA转移之前对成纤维细胞进行了基因修饰，以分泌IL-2并表达同种异体MHC I类H-2kb决定簇。仅用表达trop-1的成纤维细胞进行免疫治疗的已确诊乳腺癌小鼠，对乳腺癌细胞产生了CD8+细胞介导的免疫。这种免疫力足以延长患有乳腺癌的小鼠的生存时间。在某些情况下，这种免疫力足以导致肿瘤排斥反应；小鼠保持无肿瘤状态超过60天。
This study describes the immunotherapeutic properties of vaccines that encode tumor-associated calcium signal transducer-1 (Trop-1), a newly identified breast cancer antigen, in mice with breast cancer. Previously we found that Trop-1 was over-expressed in cellular breast cancer vaccines that were highly enriched for cells that induced therapeutic CTL-mediated immune responses in mice with breast cancer, as compared with non-enriched vaccines. In this study, to determine if the expression of Trop-1 by cells in the enriched vaccine was responsible for its therapeutic benefits, an expression plasmid that specified the Trop-1 gene was transfected into the LM fibroblast cells, which was then used as a vaccine. To augment their immunogenic properties, the fibroblasts were genetically modified before Trop-1 DNA-transfer to secrete IL-2 and to express allogeneic MHC class I H-2Kb-determinants. Mice with established breast cancer treated solely by immunization with fibroblasts modified to express Trop-1 developed CD8+cell-mediated immunity to the breast cancer cells. The immunity was sufficient to prolong the survival of mice with established breast cancer. In some instances, the immunity was sufficient to result in rejection of the tumor; the mice remained tumor free more than 60 days.