Renard Valéry, Sonderbye Lene, Ebbehøj Kirsten, Rasmussen Peter Birk, Gregorius Klaus, Gottschalk Tine, Mouritsen Søren, Gautam Anand, Leach Dana R
Pharmexa A/S, Hørsholm, Denmark.
J Immunol. 2003 Aug 1;171(3):1588-95. doi: 10.4049/jimmunol.171.3.1588.
Overexpression of the growth factor receptor HER-2 (c-erbB-2, neu) has transforming potential and occurs in approximately 20-30% of breast and ovarian cancers. HER-2 is a self Ag, but Abs and T cells specific for HER-2 have been isolated from cancer patients, suggesting HER-2 may be a good target for active immunotherapy. We constructed rat HER-2 DNA and protein vaccines containing potent Th cell epitopes derived from tetanus toxin and studied their potency in two strains of mice transgenic for the rat HER-2 molecule. Vaccination with HER-2 DNA protected nontransgenic mice from tumor challenge, but induced only moderate protection in one of the tumor models. However, vaccination with the modified HER-2 protein resulted in almost complete protection from tumor challenge in both tumor models. This protection could be mediated by Abs alone. In addition, protein vaccination efficiently eliminated pre-established tumors in both models, even when vaccination occurred 9 days after tumor implantation. These data demonstrate the potential of HER-2-based vaccines as therapeutic agents for the treatment of cancers overexpressing HER-2.
生长因子受体HER-2（c-erbB-2，neu）的过表达具有转化潜能，约20%-30%的乳腺癌和卵巢癌中会出现这种情况。HER-2是一种自身抗原，但已从癌症患者中分离出针对HER-2的抗体和T细胞，这表明HER-2可能是主动免疫治疗的良好靶点。我们构建了含有源自破伤风毒素的强效Th细胞表位的大鼠HER-2 DNA和蛋白质疫苗，并在两种转大鼠HER-2分子基因的小鼠品系中研究了它们的效力。用HER-2 DNA疫苗接种可保护非转基因小鼠免受肿瘤攻击，但在其中一个肿瘤模型中仅诱导出中等程度的保护作用。然而，用修饰后的HER-2蛋白质疫苗接种在两个肿瘤模型中均导致几乎完全免受肿瘤攻击。这种保护作用可仅由抗体介导。此外，蛋白质疫苗接种在两个模型中均能有效消除预先建立的肿瘤，即使在肿瘤植入后9天进行疫苗接种也是如此。这些数据证明了基于HER-2的疫苗作为治疗过表达HER-2癌症的治疗剂的潜力。
