Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine.
Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine.
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DOI：
10.3390/cancers13122909
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发表时间：
2021-06-10
期刊：
影响因子：
5.2
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Hu H;Steinmetz NF
病毒样颗粒（VLP）作为免疫治疗平台和癌症疫苗，用于诱导针对肿瘤的抗原特异性免疫反应，引起了人们的极大兴趣。我们通过无铜点击化学将 HER2 衍生的 CH401 表位与酸浆斑驳病毒 (PhMV) 样颗粒的外表面结合，制备了人表皮生长因子受体 2 (HER2) 癌症疫苗。另一种候选药物是通过将 Toll 样受体 9 (TLR9) 激动剂作为佐剂加载到 PhMV-CH401 的内腔中来制备的，尽管佐剂的添加不会带来额外的免疫启动。使用初免-加强免疫方案和 BALB/c 小鼠皮下注射基于 VLP 的抗 HER2 候选疫苗。该候选疫苗引发了强烈的免疫反应，包括高滴度的 HER2 特异性免疫球蛋白，并增加了抗血清对 DDHER2 肿瘤细胞的毒性。 DDHER2 肿瘤攻击研究证明了其有效性，从接种疫苗的 BALB/C 小鼠相比，接种疫苗的小鼠的肿瘤生长延迟和存活时间延长即可证明这一点。使用植物病毒样颗粒 (VLP) 平台开发人类表皮生长因子受体 2 (HER2) 特异性癌症疫苗。开发了无铜点击化学和输注封装方案来制备显示 HER2 衍生的 CH401 肽表位的 VLP，并在 VLP 的内腔中加载或不加载 Toll 样受体 9 (TLR9) 激动剂；使用基于酸浆斑驳病毒（PhMV）的VLP。通过皮下注射候选疫苗对 BALB/c 小鼠进行初免-加强免疫后，收集血清并通过酶联免疫吸附测定 (ELISA) 分析 CH401 特异性抗体； Th1 与 Th2 偏倚通过抗体亚型分析和脾细胞测定来确定。通过使用 DDHER2 肿瘤细胞进行肿瘤攻击来评估疗效。我们成功开发了两种基于VLP的抗HER2候选疫苗——PhMV-CH401与CpG-PhMV-CH401；然而，CpG 佐剂的添加并没有带来额外的免疫启动。两种基于 VLP 的候选疫苗均引发了强烈的免疫反应，包括高滴度的 HER2 特异性免疫球蛋白和抗血清对 DDHER2 肿瘤细胞的毒性增加。 DDHER2 肿瘤生长被延迟，导致接种疫苗的 BALB/C 小鼠的存活时间延长。基于 PhMV 的抗 HER2 疫苗 PhMV-CH401 已证明作为抗 HER2 癌症疫苗的功效。我们的研究强调，源自 PhMV 的 VLP 是开发癌症疫苗的一个有前景的平台。
Virus-like particles (VLPs) have attracted significant interest as immunotherapy platforms and cancer vaccines for inducing antigen-specific immune responses against tumors. We prepared a human epidermal growth factor receptor-2 (HER2) cancer vaccine, by conjugating the HER2-derived CH401 epitope to the external surface of Physalis mottle virus (PhMV)-like particles via copper-free click chemistry. Another candidate was prepared by loading Toll-like receptor 9 (TLR9) agonists as adjuvant into the interior cavity of PhMV-CH401—although the addition of the adjuvant conferred no additional immune priming. The VLP-based anti-HER2 vaccine candidate was administered subcutaneously, using a prime-boost immunization schedule and BALB/c mice. The vaccine candidate elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased the toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor challenge studies demonstrated efficacy, as evident from the delayed onset of tumor growth and the prolonged survival of the vaccinated vs. naïve BALB/C mice. To develop a human epidermal growth factor receptor-2 (HER2)-specific cancer vaccine, using a plant virus-like particle (VLP) platform. Copper-free click chemistry and infusion encapsulation protocols were developed to prepare VLPs displaying the HER2-derived CH401 peptide epitope, with and without Toll-like receptor 9 (TLR9) agonists loaded into the interior cavity of the VLPs; Physalis mottle virus (PhMV)-based VLPs were used. After prime-boost immunization of BALB/c mice through subcutaneous administration of the vaccine candidates, sera were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for the CH401-specific antibodies; Th1 vs. Th2 bias was determined by antibody subtyping and splenocyte assay. Efficacy was assessed by tumor challenge using DDHER2 tumor cells. We successful developed two VLP-based anti-HER2 vaccine candidates—PhMV-CH401 vs. CpG-PhMV-CH401; however, the addition of the CpG adjuvant did not confer additional immune priming. Both VLP-based vaccine candidates elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor growth was delayed, leading to prolonged survival of the vaccinated vs. naïve BALB/C mice. The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines.
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影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
影响因子：
168.9
作者：
Loibl, Sibylle;Gianni, Luca
通讯作者：
Gianni, Luca
DOI：
10.1016/j.nano.2018.09.004
发表时间：
2019-01
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
作者：
Neek M;Kim TI;Wang SW
通讯作者：
Wang SW
影响因子：
168.9
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
4.7
作者：
Hu H;Steinmetz NF
通讯作者：
Steinmetz NF