Shukla Sourabh, Wen Amy M, Commandeur Ulrich, Steinmetz Nicole F
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
J Mater Chem B. 2014 Oct 7;2(37):6249-6258. doi: 10.1039/c4tb00749b. Epub 2014 Aug 18.
Human epidermal growth factor receptor 2 (HER2)-positive cancers are aggressive, have poor prognoses, and have a high rate of metastasis and relapse. Immunotherapy (e.g. trastuzumab) has shown improvement in the outcome for HER2 patients. Development of drug resistance and short half-lives limiting the duration of the therapy are barriers in the development of effective therapeutic strategies. Furthermore, while passive immunotherapy provides treatment, it does not reduce the risk of recurrence of the disease. These barriers have fueled the development of active immunotherapies using HER2 vaccines. We turned toward the development of a nanoparticle-based peptide vaccine. Specifically, we integrated HER2 epitopes on the plant-produced vaccination platform potato virus X (PVX) to overcome immunological tolerance against HER2. The carrier acts as an adjuvant and improves stability and B cell presentation of the epitopes. Immunizations of FVB/N mice resulted in the production of HER2-specific antibodies, as shown by ELISA and confocal microscopy using HER2-positive human cancer cell lines.
人表皮生长因子受体2（HER2）阳性癌症具有侵袭性，预后较差，转移和复发率高。免疫疗法（如曲妥珠单抗）已显示可改善HER2患者的治疗结果。耐药性的产生以及限制治疗持续时间的短半衰期是有效治疗策略开发中的障碍。此外，虽然被动免疫疗法可提供治疗，但它并不能降低疾病复发的风险。这些障碍推动了使用HER2疫苗的主动免疫疗法的发展。我们致力于开发一种基于纳米颗粒的肽疫苗。具体而言，我们将HER2表位整合到植物生产的疫苗接种平台马铃薯X病毒（PVX）上，以克服对HER2的免疫耐受。该载体充当佐剂，提高表位的稳定性和B细胞呈递。使用HER2阳性人类癌细胞系进行的ELISA和共聚焦显微镜检测表明，对FVB/N小鼠进行免疫可产生HER2特异性抗体。
