Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells
Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells
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DOI：
10.1007/s00345-005-0505-5
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Schendel, DJ
中科院分区：
文献类型：
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作者：
Frankenberger, B;Regn, S;Schendel, DJ
肾细胞癌（RCC）的最初疫苗开发集中于基于细胞的方法，其中肿瘤细胞本身提供未知肿瘤相关抗原的混合物作为免疫剂。来源于自体肿瘤的抗原可以直接对个体肿瘤特征性的分子复合物产生应答，而来源于同种异体肿瘤细胞的抗原必须由RCC共同共享。目前已研究了三种类型的RCC细胞疫苗：分离的肿瘤细胞悬液、基因修饰的肿瘤细胞和表达RCC相关抗原的树突状细胞（DC）。使用自体RCC的遗传修饰的方法包括肿瘤细胞的离体修饰或体内肿瘤的修饰。我们已经使用同种异体肿瘤细胞系的基因修饰来创建通用RCC疫苗。最近，重点已经转移到使用DC作为RCC的基于细胞的疫苗。由于其优异的刺激能力，结合其加工抗原并将抗原呈递给初始CD4和CD8细胞的能力，DC已经移动到中心感兴趣的位置。通过使用人类基因组研究中出现的工具和信息，在确定RCC特异性免疫治疗的分子靶点方面的长期僵局正在迅速克服。使用cDNA阵列鉴定RCC表达的候选分子，结合蛋白质阵列和鉴定MHC分子呈递的肽，允许针对个体肿瘤的抗原谱定制特异性疫苗，为开发患者特异性疫苗提供基础。
Initial vaccine developments for renal cell carcinoma (RCC) have concentrated on cell-based approaches in which tumor cells themselves provide mixtures of unknown tumor-associated antigens as immunizing agents. Antigens derived from autologous tumors can direct responses to molecular composites characteristic of individual tumors, whereas antigens derived from allogeneic tumor cells must be commonly shared by RCC. Three types of cell-based vaccine for RCC have been investigated: isolated tumor cell suspensions, gene modified tumor cells and dendritic cells (DCs) expressing RCC-associated antigens. Approaches using genetic modification of autologous RCC have included ex vivo modification of tumor cells or modification of tumors in vivo. We have used gene-modification of allogeneic tumor cell lines to create generic RCC vaccines. More recently, emphasis has shifted to the use of DCs as cell-based vaccines for RCC. DCs have moved to a position of central interest because of their excellent stimulatory capacity, combined with their ability to process and present antigens to both naive CD4 and CD8 cells. The long impasse in identifying molecular targets for specific immunotherapy of RCC is now rapidly being overcome through the use of tools and information emerging from human genome research. Identification of candidate molecules expressed by RCC using cDNA arrays, combined with protein arrays and identification of peptides presented by MHC molecules, allow specific vaccines to be tailored to the antigenic profile of individual tumors, providing the basis for development of patient-specific vaccines.