Virus like particles as a platform for cancer vaccine development.
Virus like particles as a platform for cancer vaccine development.
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作者：
Ong HK;Tan WS;Ho KL
在人类历史上，癌症已经夺去了数百万人的生命，并且仍然在全世界范围内构成严重的健康问题。因此，迫切需要开发预防性和治疗性癌症疫苗。在各种癌症疫苗开发平台中，病毒样颗粒（VLP）提供了几个优势。VLP是具有类似于天然病毒的形态的多聚体纳米结构，并且主要由病毒的表面结构蛋白组成，但缺乏病毒遗传物质，使得它们既不具有感染性也不具有复制性。此外，它们可以被工程化以展示多个高度有序的异源表位或肽，以优化展示实体的抗原性和免疫原性。与天然病毒一样，VLP上展示的特异性表位可以被抗原呈递细胞摄取、加工和呈递，以引发有效的特异性体液和细胞介导的免疫应答。几项研究还表明，VLP可以克服肿瘤微环境的免疫抑制状态，并打破自身耐受性，以引起强烈的细胞毒性淋巴细胞活性，这对于病毒清除和癌细胞的破坏都是至关重要的。总的来说，VLP的这些独特特征使它们成为最佳的癌症疫苗候选者。本文就VLP在肿瘤疫苗研究中的应用进展以及VLP在肿瘤疫苗研究中存在的问题作一综述。与病毒颗粒相似的细胞外囊泡也被讨论，并与VLP作为癌症疫苗开发的平台进行比较。
Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative. In addition, they can be engineered to display multiple, highly ordered heterologous epitopes or peptides in order to optimize the antigenicity and immunogenicity of the displayed entities. Like native viruses, specific epitopes displayed on VLPs can be taken up, processed, and presented by antigen-presenting cells to elicit potent specific humoral and cell-mediated immune responses. Several studies also indicated that VLPs could overcome the immunosuppressive state of the tumor microenvironment and break self-tolerance to elicit strong cytotoxic lymphocyte activity, which is crucial for both virus clearance and destruction of cancerous cells. Collectively, these unique characteristics of VLPs make them optimal cancer vaccine candidates. This review discusses current progress in the development of VLP-based cancer vaccines and some potential drawbacks of VLPs in cancer vaccine development. Extracellular vesicles with close resembling to viral particles are also discussed and compared with VLPs as a platform in cancer vaccine developments.
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