Aura Biosciences, Cambridge, MA 02140, USA.
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Viruses. 2022 Jul 28;14(8):1656. doi: 10.3390/v14081656.
Human papillomaviruses (HPV) are small non-enveloped DNA tumor viruses established as the primary etiological agent for the development of cervical cancer. Decades of research have elucidated HPV's primary attachment factor to be heparan sulfate proteoglycans (HSPG). Importantly, wounding and exposure of the epithelial basement membrane was found to be pivotal for efficient attachment and infection of HPV in vivo. Sulfation patterns on HSPG's become modified at the site of wounds as they serve an important role promoting tissue healing, cell proliferation and neovascularization and it is these modifications recognized by HPV. Analogous HSPG modification patterns can be found on tumor cells as they too require the aforementioned processes to grow and metastasize. Although targeting tumor associated HSPG is not a novel concept, the use of HPV to target and treat tumors has only been realized in recent years. The work herein describes how decades of basic HPV research has culminated in the rational design of an HPV-based virus-like infrared light activated dye conjugate for the treatment of choroidal melanoma.
人乳头瘤病毒（HPV）是小型无包膜 DNA 肿瘤病毒，已被确立为宫颈癌发展的主要病因。数十年的研究阐明了 HPV 的主要附着因子是硫酸乙酰肝素蛋白聚糖（HSPG）。重要的是，研究发现上皮基底膜的创伤和暴露对于 HPV 在体内的有效附着和感染至关重要。HSPG 上的硫酸化模式在创伤部位发生改变，因为它们在促进组织愈合、细胞增殖和新血管生成方面发挥着重要作用，而 HPV 正是识别这些修饰。肿瘤细胞上也存在类似的 HSPG 修饰模式，因为它们的生长和转移也需要上述过程。尽管针对肿瘤相关 HSPG 并不是一个新的概念，但近年来才意识到利用 HPV 来靶向和治疗肿瘤。本文描述了数十年的 HPV 基础研究如何最终促成了基于 HPV 的病毒样近红外光激活染料偶联物的合理设计，用于治疗脉络膜黑色素瘤。
