Guo Wei, Guo Yi, Tang Shun, Qu Huayi, Zhao Hui
Musculoskeletal Tumor Center, Peking University People's Hospital, #11 South Xizhimen Street, Beijing 100044, People's Republic of China.
Clin Orthop Relat Res. 2008 Sep;466(9):2176-83. doi: 10.1007/s11999-008-0348-7. Epub 2008 Jun 19.
Given the effective immunotherapy of DC-based vaccine in other cancers, we hypothesized DC-based vaccines would induce effective immune responses against Ewing's sarcoma. To verify this hypothesis and develop the most effective dendritic cell vaccine against Ewing's sarcoma, we evaluated the antitumor efficacy of dendritic cell-Ewing's sarcoma hybrids and dendritic cells pulsed with other antigen-loading methods, including cell lysates and the characteristic EWS-FLI1 gene of Ewing's sarcoma, using an A673 cell line as a model. The hybrids were generated by electrofusion with fusion efficiency and viability determined by flow cytometry and fluorescent microscopy analyses. By interferon-gamma secretion assay, the capacity of hybrids to stimulate cytotoxic T-lymphocytes (CTLs) is higher than that of other antigen-loading methods showing stronger tumor antigen-specific CTL cytotoxicity to A673. By in vivo experiment in SCID mice, all dendritic cell-based strategies induced specific immune responses to Ewing's sarcoma after mice-human immune system reconstitution by inoculating human peripheral blood mononuclear cells into the peritoneal cavity of SCID mice. However, the hybrids most inhibited the subcutaneous tumor growth in SCID mice compared with dendritic cells pulsed with other loading methods. The data suggest A673 cells respond to dendritic cell-based immunotherapy.
鉴于基于树突状细胞（DC）的疫苗在其他癌症中具有有效的免疫治疗作用，我们推测基于DC的疫苗会诱导针对尤因肉瘤的有效免疫反应。为了验证这一假设并开发出针对尤因肉瘤最有效的树突状细胞疫苗，我们以A673细胞系为模型，评估了树突状细胞-尤因肉瘤杂交细胞以及采用其他抗原负载方法（包括细胞裂解物和尤因肉瘤特征性EWS-FLI1基因）脉冲处理的树突状细胞的抗肿瘤效果。杂交细胞通过电融合产生，其融合效率和活力通过流式细胞术和荧光显微镜分析来确定。通过干扰素-γ分泌测定，杂交细胞刺激细胞毒性T淋巴细胞（CTL）的能力高于其他抗原负载方法，对A673显示出更强的肿瘤抗原特异性CTL细胞毒性。通过在SCID小鼠体内进行的实验，在将人外周血单个核细胞接种到SCID小鼠腹腔进行人-小鼠免疫系统重建后，所有基于树突状细胞的策略均诱导了针对尤因肉瘤的特异性免疫反应。然而，与采用其他负载方法脉冲处理的树突状细胞相比，杂交细胞对SCID小鼠皮下肿瘤生长的抑制作用最强。数据表明A673细胞对基于树突状细胞的免疫治疗有反应。
