Breast cancer is a worldwide health problem, and the complexity of the disease, as well as the lack of treatment specificity, generates an urgent need for developing prophylactic and therapeutic measures. Searching for novel epitope-based approaches able to induce tumour immunity, we designed virus-like particles (VLPs) derived from Human parvovirus B19 assembled of chimeric VP2 proteins displaying two epitopes from the insulin-like growth factor-1 receptor (IGF-1R). Here, we present the generation of two chimeric VP2s that retain the stability, solubility and conditions of purification and assembly of the native VP2. We generated versatile chimeric multiepitope anti-cancer vaccine candidates, which prevented and delayed tumour growth when used in a prophylactic scheme of 4 weekly immunizations prior to 4T1 cell inoculation in female BALB/c mice. The presence of specific antibodies against the displayed epitopes suggests their participation in the protective effect; in contrast, no significant proliferative T-cell responses were recorded following stimulation by specific epitopes. The results comprise an approach whereby fusing desired epitopes from cancer to the N-terminus of B19 VP2 protein can generate a library of chimeric VP2-desired epitopes for further assembly in a designed and personalized epitope delivery system.

中文翻译：

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在嵌合人细小病毒B19病毒样颗粒中靶向IGF-1受体的乳腺癌相关表位的表达。

乳腺癌是世界范围内的健康问题，并且疾病的复杂性以及缺乏治疗特异性导致迫切需要开发预防和治疗措施。为了寻找能够诱导肿瘤免疫的新的基于抗原决定簇的方法，我们设计了人类细小病毒B19衍生的病毒样颗粒（VLP），该病毒由嵌合VP2蛋白组装而成，展示了胰岛素样生长因子-1受体（IGF-1R）的两个表位。在这里，我们介绍了两个嵌合VP2的生成，它们保留了天然VP2的稳定性，溶解性以及纯化和组装的条件。我们生成了多功能嵌合多表位抗癌疫苗候选物，当在雌性BALB / c小鼠中接种4T1细胞之前的4周免疫接种的预防方案中使用时，它可以预防和延迟肿瘤的生长。针对展示的表位的特异性抗体的存在表明它们参与了保护作用。相反，在被特定表位刺激后，没有记录到明显的增殖性T细胞应答。结果包括一种方法，通过该方法将所需的癌症抗原决定簇融合到B19 VP2蛋白的N末端可以生成嵌合VP2所需抗原决定簇的文库，以进一步组装在设计和个性化的抗原决定簇递送系统中。