Expression of Breast Cancer-Related Epitopes Targeting the IGF-1 Receptor in Chimeric Human Parvovirus B19 Virus-Like Particles
Expression of Breast Cancer-Related Epitopes Targeting the IGF-1 Receptor in Chimeric Human Parvovirus B19 Virus-Like Particles
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DOI：
10.1007/s12033-019-00198-y
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发表时间：
2019-10-01
影响因子：
2.6
通讯作者：
Moreno-Fierros, Leticia
中科院分区：
文献类型：
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作者：
Alberto Salazar-Gonzalez, Jorge;Antonio Ruiz-Cruz, Alail;Moreno-Fierros, Leticia
乳腺癌是一个全球性的健康问题，由于该疾病的复杂性以及缺乏治疗特异性，迫切需要制定预防和治疗措施。为了寻找能够诱导肿瘤免疫的基于表位的新方法，我们设计了来自人细小病毒B19的病毒样颗粒（VLPs），该颗粒由嵌合VP2蛋白组装而成，显示来自胰岛素样生长因子-1受体（IGF-1R）的两个表位。在这里，我们提出了两个嵌合VP2s的产生，它们保留了天然VP2的稳定性，溶解度和纯化和组装条件。我们制备了多功能嵌合多表位抗癌候选疫苗，在雌性BALB/c小鼠中，在4T1细胞接种之前，将其用于预防方案，即每周免疫4次，以防止和延迟肿瘤生长。针对所显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，在特定表位刺激后，没有记录到显著的增殖t细胞反应。结果包括一种方法，该方法将来自癌症的所需表位融合到B19 VP2蛋白的n端，可以产生嵌合VP2所需表位库，以便在设计和个性化的表位传递系统中进一步组装。
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.