Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy.
Breast J. 2010 Sep-Oct;16 Suppl 1:S39-41. doi: 10.1111/j.1524-4741.2010.01002.x.
Cancer immunoprevention posits that the enhancement of immune defenses in healthy individuals could control tumor onset. Immunoprevention of viral tumors is already implemented at the population level for human hepatocellular and cervical carcinomas. Altogether, viral vaccines could prevent more than 10% of all human tumors. The big question is whether immunoprevention can be applied to nonviral tumors, including breast cancer. Promising results were obtained in preclinical models, in particular in HER-2/neu transgenic mice, which are prone to mammary carcinoma development, using vaccines against HER-2/neu oncoprotein p185. The life expectancy of vaccinated mice was more than doubled. Protective immune mechanisms elicited by effective vaccines were mainly based on helper T cell cytokines, in particular γ-interferon, and anti-p185 antibodies. The term "oncoantigens" was coined to define those antigenic molecules that, like HER-2, are indispensable for tumor growth, thus representing the best class of targets for cancer immunoprevention. The study of immunopreventive vaccines against subsequent phases of neoplastic progression showed a dramatic loss of efficacy against established mammary carcinomas, whereas the prevention of micrometastasis growth was successful. Preclinical results provide useful indications for the translation of cancer immunoprevention to humans, and useful hints for cancer immunotherapy.
癌症免疫预防假设，在健康个体中增强免疫防御能力可以控制肿瘤的发生。针对人类肝细胞癌和宫颈癌，已经在人群层面上实施了病毒肿瘤的免疫预防。总的来说，病毒疫苗可以预防超过 10%的人类肿瘤。最大的问题是，免疫预防是否可以应用于非病毒肿瘤，包括乳腺癌。在临床前模型中，特别是在易患乳腺癌的 HER-2/neu 转基因小鼠中，使用针对 HER-2/neu 癌蛋白 p185 的疫苗已经取得了有希望的结果。接种疫苗的小鼠的预期寿命增加了一倍以上。有效疫苗引发的保护性免疫机制主要基于辅助性 T 细胞细胞因子，特别是 γ-干扰素和抗 p185 抗体。“肿瘤相关抗原”一词被用来定义那些像 HER-2 一样对肿瘤生长必不可少的抗原分子，因此代表了癌症免疫预防的最佳靶标类别。对针对肿瘤进展后续阶段的免疫预防疫苗的研究表明，针对已建立的乳腺癌的疗效显著降低，而预防微转移生长则取得了成功。临床前结果为将癌症免疫预防转化为人类提供了有用的指示，并为癌症免疫治疗提供了有用的提示。
