Yokomine Kazunori, Nakatsura Tetsuya, Minohara Motozumi, Kira Jun-ichi, Kubo Tatsuko, Sasaki Yutaka, Nishimura Yasuharu
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Biochem Biophys Res Commun. 2006 Apr 28;343(1):269-78. doi: 10.1016/j.bbrc.2006.02.142. Epub 2006 Mar 3.
Recently, we reported that heat shock protein 105 (HSP105) DNA vaccination induced anti-tumor immunity. In this study, we set up a preclinical study to investigate the usefulness of dendritic cells (DCs) pulsed with mouse HSP105 as a whole protein for cancer immunotherapy in vivo. The recombinant HSP105 did not induce DC maturation, and the mice vaccinated with HSP105-pulsed BM-DCs were markedly prevented from the growth of subcutaneous tumors, accompanied with a massive infiltration of both CD4+ T cells and CD8+ T cells into the tumors. In depletion experiments, we proved that both CD4+ T cells and CD8+ T cells play a crucial role in anti-tumor immunity. Both CD4+ T cells and CD8+ T cells specific to HSP105 were induced by stimulation with HSP105-pulsed DCs. As a result, vaccination of mice with BM-DCs pulsed with HSP105 itself could elicit a stronger tumor rejection in comparison to DNA vaccination.
最近,我们报道了热休克蛋白105(HSP105)DNA疫苗可诱导抗肿瘤免疫。在本研究中,我们开展了一项临床前研究,以探究用小鼠HSP105全蛋白脉冲处理的树突状细胞(DCs)在体内癌症免疫治疗中的效用。重组HSP105未诱导DC成熟,接种HSP105脉冲处理的骨髓来源DCs(BM-DCs)的小鼠皮下肿瘤生长明显受到抑制,同时肿瘤内有大量CD4⁺ T细胞和CD8⁺ T细胞浸润。在清除实验中,我们证明CD4⁺ T细胞和CD8⁺ T细胞在抗肿瘤免疫中均发挥关键作用。用HSP105脉冲处理的DCs刺激可诱导产生针对HSP105的CD4⁺ T细胞和CD8⁺ T细胞。结果,与DNA疫苗接种相比,用HSP105自身脉冲处理的BM-DCs对小鼠进行疫苗接种可引发更强的肿瘤排斥反应。