Kieber-Emmons T, Luo P, Qiu J, Chang T Y, O I, Blaszczyk-Thurin M, Steplewski Z
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Nat Biotechnol. 1999 Jul;17(7):660-5. doi: 10.1038/10870.
Tumor-associated carbohydrate (TAC) antigens are important targets in cancer vaccine efforts. Carbohydrates are, however, frequently poor immunogens, in that they are T-cell-independent antigens. Molecular mimicry of TAC by peptides is an alternative approach to generating anti-carbohydrate immune responses. Here we demonstrate that peptide mimotopes can elicit antibody responses that cross-react with representative human TAC antigens. Primary immunization with such a multiple antigenic peptide, along with QS-21 as adjuvant, elicits cytotoxic antibodies reactive with naturally occurring forms of TAC expressed on tumor cells, and vaccination of mice with peptide mimotopes reduced tumor growth and prolonged host survival in a murine tumor model.
肿瘤相关碳水化合物(TAC)抗原是癌症疫苗研发中的重要靶点。然而,碳水化合物通常是较差的免疫原,因为它们是不依赖T细胞的抗原。通过肽对TAC进行分子模拟是产生抗碳水化合物免疫反应的一种替代方法。在此,我们证明肽模拟表位可引发与代表性人类TAC抗原发生交叉反应的抗体反应。用这种多抗原肽进行初次免疫,并辅以QS-21作为佐剂,可引发与肿瘤细胞上天然存在形式的TAC发生反应的细胞毒性抗体,并且在小鼠肿瘤模型中用肽模拟表位对小鼠进行疫苗接种可减少肿瘤生长并延长宿主存活时间。