HER-2/neu表位肿瘤疫苗研究进展

Advanced of HER-2/neu epitope anti-tumor vaccine

原癌基因HER-2/neu(human epidermal growth factor receptor type 2)在乳腺癌(20%~40%)、结直肠癌(54%~100%)、卵巢癌(25%)等多种肿瘤中有扩增或过表达,故HER-2/neu蛋白是肿瘤候选靶标抗原之一,且已被证明具有开发抗乳腺癌疫苗的潜力。目前针对不同类型的HER-2疫苗,包括全细胞疫苗、全序列蛋白疫苗、肽疫苗、树突状细胞(DC)相关疫苗以及基因疫苗等展开了一系列研究,并取得一定进展。该文通过检索百度学术,PubMed,Springer以及ScienceDirect数据库,对近年来HER-2/neu肿瘤疫苗的制备及其抗肿瘤活性机制的研究进展进行综述。HER-2/neu肿瘤疫苗经抗原递呈细胞(APCs)展示,能够有效地激活CD4^+T和CD8^+T,并诱导特异性抗肿瘤免疫应答反应,其结构及组成佐剂的改变、融合表达以及DC诱导等疫苗设计工艺改变,能够显著地提高疫苗的免疫活性和抗肿瘤活性。HER-2疫苗在临床试验研究中发现能够有效地降低抗体药物治疗所致的耐药性,反复用药以及其它化疗药物的严重毒副作用等缺陷,并有效稳定地发挥抗肿瘤活性,为肿瘤的治疗提供一个崭新的视角。

Overexpression of HER-2/neu oncogene is a frequent molecular event in multiple human cancer,including breast cancer(20%-40%),colorectal cancer(54%-100%),ovarian cancer(25%).Therefore,HER-2/neu protein is one of the candidate target antigens for cancer,and has been proved to have the potential to develop anti-breast cancer vaccines.At present,a series of studies have been carried out on different types of HER-2 vaccines,including whole-cell vaccines,full-sequence protein vaccines,peptide vaccines and DC-induced vaccines,and some progress has been made.A baidu Scholar,PubMed,Springer and ScienceDirect database search was performed to review the advanced of the preparation technology and the mechanism of antineoplastic activity of tumor vaccine based on HER-2/neu antigen.As the conclusions shown in the present paper,CD4^+T and CD8^+T were activated successfully and the anti-tumor specific immune response was induced by the antigen presenting cells(APCs)presented with the HER-2/neu tumor vaccine antigenic epitope.The immunological and anti-tumor activity would be improved by the change of vaccine design process,such as the reform of composition structure,fusion expression with immune-boosting short peptides and dendritic cell induced.The defect of drug resistance and repeated administration accompanied by HER-2 monoclonal antibody treatment and the serious toxicity of traditional chemotherapy drugs treatment could be reduced by HER-2 anti-tumor vaccine treatment with the stable anti-tumor activity in the clinic trail,which would provide a new perspective of tumor treatment.