Schreurs M W, de Boer A J, Figdor C G, Adema G J
Department of Tumor Immunology, University Hospital Nijmegen St. Radboud, The Netherlands.
Cancer Res. 1998 Jun 15;58(12):2509-14.
Melanocyte lineage-specific antigens, such as gp100, have been shown to induce both cellular and humoral immune responses against melanoma. Therefore, these antigens are potential targets for specific antimelanoma immunotherapy. A novel approach to induce both cellular and humoral immunity is genetic vaccination, the injection of antigen-encoding naked plasmid DNA. In a mouse model, we investigated whether genetic vaccination against the human gp100 antigen results in specific antitumor immunity. The results demonstrate that vaccinated mice were protected against a lethal challenge with syngeneic B16 melanoma-expressing human gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific for human gp100 could be detected in human gp100-vaccinated mice. However, only adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from protected mice was able to transfer antitumor immunity to nonvaccinated recipients, indicating that CTLs are the predominant effector cells. CTI, lines generated from human gp100-vaccinated mice specifically recognized human gp100. Interestingly, one of the CTL lines cross-reacted between human and mouse gp100, indicating the recognition of a conserved epitope. However, these CTLs did not appear to be involved in the observed tumor protection. Collectively, our results indicate that genetic vaccination can result in a potent antitumor response in vivo and constitutes a potential immunotherapeutic strategy to fight cancer.
黑色素细胞谱系特异性抗原，如糖蛋白100（gp100），已被证明能诱导针对黑色素瘤的细胞免疫和体液免疫反应。因此，这些抗原是特异性抗黑色素瘤免疫疗法的潜在靶点。一种诱导细胞免疫和体液免疫的新方法是基因疫苗接种，即注射编码抗原的裸质粒DNA。在小鼠模型中，我们研究了针对人类gp100抗原的基因疫苗接种是否能产生特异性抗肿瘤免疫。结果表明，接种疫苗的小鼠受到了表达人类gp100的同基因B16黑色素瘤的致死性攻击的保护，但未受到对照转染的B16的保护。在接种人类gp100的小鼠中可以检测到针对人类gp100的细胞毒性T细胞和IgG。然而，只有从受保护小鼠中分离出的脾源淋巴细胞的过继转移，而不是血清的过继转移，能够将抗肿瘤免疫转移给未接种疫苗的受体，这表明细胞毒性T淋巴细胞（CTLs）是主要的效应细胞。从接种人类gp100的小鼠中产生的CTL系特异性识别人类gp100。有趣的是，其中一个CTL系在人类和小鼠gp100之间发生交叉反应，表明识别了一个保守表位。然而，这些CTL似乎并未参与观察到的肿瘤保护作用。总的来说，我们的结果表明基因疫苗接种可以在体内产生有效的抗肿瘤反应，并构成一种潜在的抗癌免疫治疗策略。
