Zhao Hui, Tang Shun, Qu Hua Yi, Guo Wei, Li Xiao, Peng Chang Liang
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2007 Aug 18;39(4):403-8.
To compare the efficacy of different immunotherapeutic strategies of loading dendritic cells (DCs) with the antigen of the Ewing sarcoma in vitro and in vivo.
DCs were either electrofused with the whole Ewing sarcoma cells A673, pulsed with lysates of the tumor cell or modified with the characteristic EWS/FLI1 gene. Then we assessed the capacity of the stimulated cytoxicity T lymphocyte (CTLs) by the parameter of the interferon-gamma (IFN-gamma) secreted and the cytotoxicity to the A673. In vivo experiment, the human IgG serum concentrations of the SCID mice were measured to determine the mouse human immune system reconstitution, and the growths of the inoculated tumor were measured to assess the anti-tumor effect.
The data revealed that various DC-based strategies could induce specific immune responses to the tumor, with the hybrids showing superiority to the other strategies while there were no significant differences between the sets of the gene modified DCs and non-manipulated DCs in the cytotoxicity assay to A673 cells. Moreover, there were no significant differences among the sets of the gene modified DCs, lysate pulsed DCs and non-manipulated in vivo anti-tumor effect about the tumor volume on the SCID mice.
The Ewing sarcoma had good responses to the DC-based immunotherapy and based on this experiment, we could also conclude that the product of electrofusion may be an optimal strategy for immunotherapy of Ewing sarcoma.
比较体外和体内用尤因肉瘤抗原负载树突状细胞(DCs)的不同免疫治疗策略的疗效。
将DCs与完整的尤因肉瘤细胞A673进行电融合,用肿瘤细胞裂解物脉冲处理,或用特征性的EWS/FLI1基因进行修饰。然后我们通过分泌的干扰素-γ(IFN-γ)参数和对A673的细胞毒性来评估刺激的细胞毒性T淋巴细胞(CTLs)的能力。在体内实验中,测量SCID小鼠的人IgG血清浓度以确定小鼠人免疫系统的重建,并测量接种肿瘤的生长以评估抗肿瘤效果。
数据显示,各种基于DC的策略均可诱导对肿瘤的特异性免疫反应,杂交体显示出优于其他策略,而在对A673细胞的细胞毒性测定中,基因修饰的DC组与未处理的DC组之间无显著差异。此外,在SCID小鼠上,基因修饰的DC组、裂解物脉冲处理的DC组和未处理的组在体内抗肿瘤效果方面,关于肿瘤体积没有显著差异。
尤因肉瘤对基于DC的免疫治疗有良好反应,基于本实验,我们还可以得出结论,电融合产物可能是尤因肉瘤免疫治疗的最佳策略。