Ashley D M, Faiola B, Nair S, Hale L P, Bigner D D, Gilboa E
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Exp Med. 1997 Oct 6;186(7):1177-82. doi: 10.1084/jem.186.7.1177.
Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene-modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow-generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors.
最近的研究表明,对于使用基因改造的自体肿瘤细胞疫苗的成功主动免疫疗法而言,大脑并非障碍。在本研究中,我们比较了两种疫苗治疗中枢神经系统(CNS)肿瘤的疗效:用肿瘤提取物或肿瘤RNA脉冲处理的基于树突状细胞(DC)的疫苗,以及细胞因子基因改造的肿瘤疫苗。以B16/F10小鼠黑色素瘤(B16)作为CNS肿瘤模型,我们发现用B16细胞提取物或B16总RNA脉冲处理的骨髓生成的DC进行疫苗接种,可诱导针对B16肿瘤细胞的特异性细胞毒性T淋巴细胞。两种类型的DC疫苗均能保护动物免受位于CNS的肿瘤侵害。基于DC的疫苗还能使在疫苗治疗开始前就已出现肿瘤的小鼠存活时间延长。基于DC的疫苗至少与含有已改造粒细胞巨噬细胞集落刺激因子基因的B16肿瘤细胞的疫苗一样有效,甚至可能更有效。这些数据支持使用基于DC的疫苗治疗CNS肿瘤患者。