Kwak Larry W
National Institutes of Health, USA.
Int J Hematol. 2002 Aug;76 Suppl 1:320-1. doi: 10.1007/BF03165274.
The B-cell tumor-derived Ig receptor may be considered a model tumor antigen for cancer vaccine development. However, as a non-immunogenic, self-antigen, it also must be first rendered immunogenic by chemical or genetic fusion to carriers which enable the induction of protective antitumor immunity in experimental tumor models. Our group has demonstrated that active immunization of human patients with idiotypic protein vaccines containing soluble GM-CSF elicited antigen specific CD8+ T cell responses and antitumor effects. An alternative strategy to develop vaccines is the genetic fusion of tumor idiotype-derived single chain antigen with a chemokine moiety. Administration of these vaccines as fusion proteins or naked DNA vaccines may allow more efficient targeting of antigen presenting cells in vivo. Potent antitumor immunity was elicited in mice which was dependent on the generation of specific antibodies and both CD4+ and CD8+ effector T-cells. We propose that chemokine fusion may represent a novel, general strategy for formulating existing or newly identified tumor and HIV antigens into vaccines for cancer and AIDS, respectively, which elicit potent CD8+ T-cell immunity.
B细胞肿瘤衍生的Ig受体可被视为癌症疫苗开发的一种模型肿瘤抗原。然而，作为一种非免疫原性的自身抗原，它首先必须通过与载体进行化学或基因融合使其具有免疫原性，从而在实验性肿瘤模型中诱导产生保护性抗肿瘤免疫。我们的研究小组已经证明，用含有可溶性GM-CSF的独特型蛋白疫苗对人类患者进行主动免疫可引发抗原特异性CD8+ T细胞反应和抗肿瘤效应。开发疫苗的另一种策略是将肿瘤独特型衍生的单链抗原与趋化因子部分进行基因融合。将这些疫苗作为融合蛋白或裸DNA疫苗给药可能会在体内更有效地靶向抗原呈递细胞。在小鼠中引发了强大的抗肿瘤免疫，这依赖于特异性抗体以及CD4+和CD8+效应T细胞的产生。我们提出，趋化因子融合可能代表一种新的通用策略，分别将现有的或新发现的肿瘤和HIV抗原制成用于癌症和艾滋病的疫苗，从而引发强大的CD8+ T细胞免疫。
