Nika Lisa, Cuadrado-Castano Sara, Asthagiri Arunkumar Guha, Grünwald-Gruber Clemens, McMahon Meagan, Koczka Krisztina, García-Sastre Adolfo, Krammer Florian, Grabherr Reingard
Department of Biotechnology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
Vaccines (Basel). 2019 May 20;7(2):41. doi: 10.3390/vaccines7020041.
Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in 9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigen-displaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigen-displaying VLPs produced in 9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.
人表皮生长因子受体2（HER2）在20%至30%的乳腺癌中呈上调状态，是预后不良的一个标志物。由于对曲妥珠单抗被动免疫疗法产生耐药性，能够潜在触发持久肿瘤特异性免疫反应的主动抗HER2疫苗接种策略已成为一个有吸引力的研究领域。最近，我们已经表明在昆虫细胞中产生的芽生病毒样颗粒（VLP）是表达复杂膜蛋白的理想平台。为了评估展示抗原的VLP作为主动癌症疫苗的疗效，将BALB/c小鼠用昆虫细胞糖基化和类哺乳动物糖基化的展示HER2的VLP与两种不同佐剂联合免疫，并接种HER2阳性肿瘤。与类哺乳动物糖基化的对应物相比，用昆虫细胞糖基化的HER2 VLP免疫的小鼠诱导出更高的HER2特异性抗体滴度和效应功能。此外，昆虫细胞糖基化的HER2 VLP在接种HER2阳性乳腺癌细胞的小鼠中引发了保护作用。有趣的是，在用聚肌苷酸-聚胞苷酸（Poly (I:C)）作为佐剂的小鼠中未观察到保护作用。在此，我们表明在昆虫细胞中产生的展示抗原的VLP能够在体内诱导强大而持久的免疫反应，并有潜力用作主动癌症疫苗。
