HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy

M. Omabe, Shahid Ahmed, A. Sami, Yufeng Xie, M. Tao, J. Xiang
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引用次数: 6

Abstract

Anti-human epidermal growth factor receptor-2 (HER2) immunization can be elicited by vaccination with DNA encoding the extra- or intra-cellular domain (ECD or ICD) of HER2, naked or encap-sulated in viral vectors. HER2-peptides derived from ECD or ICD of HER2, and HER2-pulsed dendritic cells (DCs) or engineered DCs expressing HER2, respectively. We performed a computer- based literature search which includes but is not limited to the following keywords: breast cancer, immunotherapy, HER2-peptide vaccine, HER2-DNA vaccine, HER-DC vaccine, HER2 vaccine, and HER2/neu, in PubMed, Medline, EMBO and Google Scholar; data from recently reported clinical trials were also included. Drawing upon this synthesis of literature, this work summarizes the de-velopment and current trend in experimental and clinical investigations in HER2-positive breast cancer using HER2-specific vaccine and immunotherapy, focusing especially on: (i) DNA-; (ii) peptide-; and (iii) DC-based vaccines. It addresses interventions that have been applied to overcome immunotolerance thereby to improve treatment outcomes. These include blocking the inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4), which is expressed at high levels by regulatory T (Treg) cells, or complete Treg depletion to improve T-cell activation. Moreover, modulatory interventions can provide further improvement in the efficacy of HER2-specific vaccine. The interventions include the use of immunogenic adjuvants such as cytokines interleukin-12 (IL-12), tumor necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF), the use of Toll-like receptor (TLR) ligands and tetanus toxin’s universal epitopes such as the CD4+ help T (Th)-epitope P30, and the use of either chimeric or heterogenous xenogeneic HER2. Combining active HER2-vaccination with adoptive trastuzumab antibody immunotherapy is likely to increase the effectiveness of each approach alone. The development of effective HER2-vaccines for breast cancer remains a critical challenge. Though these novel interventions seem promising, further investigation is still needed since the results are preliminary. Furthermore, the review discusses the challenges and future perspectives in HER2-vaccine research and development.
her2阳性乳腺癌免疫治疗的her2特异性疫苗
抗人表皮生长因子受体2 (HER2)免疫可以通过接种编码HER2细胞外或细胞内结构域(ECD或ICD)的DNA,裸或包封在病毒载体中引起。HER2肽分别来源于HER2的ECD或ICD, HER2脉冲树突状细胞(dc)或表达HER2的工程树突状细胞。我们在PubMed, Medline, EMBO和谷歌Scholar中进行了基于计算机的文献检索,包括但不限于以下关键词:乳腺癌,免疫治疗,HER2肽疫苗,HER2- dna疫苗,HER-DC疫苗,HER2疫苗和HER2/neu;最近报道的临床试验数据也包括在内。根据这些文献的综合,本工作总结了使用her2特异性疫苗和免疫疗法治疗her2阳性乳腺癌的实验和临床研究的进展和当前趋势,特别关注:(i) DNA-;(2)肽-;(三)dc型疫苗。它涉及已用于克服免疫耐受从而改善治疗结果的干预措施。这些措施包括阻断抑制性细胞毒性T淋巴细胞相关蛋白4 (CTLA-4),该蛋白在调节性T细胞(Treg)中高水平表达,或完全耗尽Treg以改善T细胞活化。此外,调节性干预可以进一步提高her2特异性疫苗的疗效。干预措施包括使用免疫原性佐剂,如细胞因子白介素-12 (IL-12)、肿瘤坏死因子(TNF)-α和粒细胞-巨噬细胞集落刺激因子(GM-CSF),使用toll样受体(TLR)配体和破伤风毒素的通用表位,如CD4+帮助T (Th)-表位P30,以及使用嵌合或异质HER2。结合活动性her2疫苗接种和过继性曲妥珠单抗抗体免疫治疗可能会增加每种方法的有效性。开发有效的乳腺癌her2疫苗仍然是一项重大挑战。虽然这些新的干预措施看起来很有希望,但由于结果是初步的,还需要进一步的调查。此外,本文还讨论了her2疫苗研究和开发的挑战和未来前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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