Vaccination against prostate cancer using a live tissue factor deficient cell line in Lobund-Wistar rats.
Vaccination against prostate cancer using a live tissue factor deficient cell line in Lobund-Wistar rats.
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使用 Lobund-Wistar 大鼠体内缺乏组织因子的活细胞系进行前列腺癌疫苗接种。
DOI：
10.1007/s00262-006-0223-x
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Suckow,MarkA
中科院分区：
文献类型：
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作者：
Heinrich,JulieE;Pollard,Morris;Wolter,WilliamA;Liang,Zhong;Song,Hui;Rosen,ElliotD;Suckow,MarkA
减少前列腺腺癌细胞（PAIII）中组织因子基因的表达导致在体内模拟野生型（wt）PAIII生长的细胞系。然而，组织因子缺陷型PAIII（TFD PAIII）肿块在数周后自发消退，而不是像wt PAIII肿瘤那样继续生长和转移。尽管全细胞疫苗通常在施用前灭活以防止宿主内的增殖，但许多研究表明，暴露于活的减毒全肿瘤细胞及其募集的细胞外微环境可增加免疫原性潜力。在这里，我们提供了支持这一概念，并通过它来实现它的策略，通过证明皮下接种TFD PAIII保护Lobund-Wistar大鼠对随后的WT PAIII细胞的挑战。与未接种疫苗的幼稚对照大鼠相比，TFD PAIII免疫的大鼠遭受wt PAIII攻击肿瘤的显著更少的转移。这些结果提供了一种有趣的可能性，即TFD PAIII疫苗是预防和可能治疗前列腺癌的有效系统。
Reducing expression of the tissue factor gene in prostate adenocarcinoma cells (PAIII) results in a cell line that, in vivo, mimics the growth of wildtype (wt) PAIII. However, instead of continuing to grow and metastasize as wt PAIII tumors do, tissue factor deficient PAIII (TFD PAIII) masses spontaneously regress after several weeks. Although whole cell vaccines are typically inactivated prior to administration to prevent proliferation within the host, numerous studies have suggested that exposure to live, attenuated, whole tumor cells, and the extracellular microenvironment they recruit, increases immunotherapeutic potential. Here, we provide support for this notion, and a strategy through which to implement it, by demonstrating that subcutaneous vaccinations with the TFD PAIII protect the Lobund–Wistar rat against subsequent wt PAIII cell challenge. TFD PAIII immunized rats suffered significantly less metastasis of wt PAIII challenge tumors compared to unvaccinated naïve controls rats. These results offer the intriguing possibility that the TFD PAIII vaccine is an effective system for the prevention and, possibly, the treatment of prostate cancer.