聚糖包裹的病毒样颗粒促进1型抗肿瘤免疫。
Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.
作者信息
Lensch Valerie, Gabba Adele, Hincapie Robert, Bhagchandani Sachin H, Basak Ankit, Alam Mohammad Murshid, Irvine Darrell J, Shalek Alex K, Johnson Jeremiah A, Finn M G, Kiessling Laura L
机构信息
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
出版信息
bioRxiv. 2024 Jan 18:2024.01.18.575711. doi: 10.1101/2024.01.18.575711.
Cancer vaccine development is inhibited by a lack of strategies for directing dendritic cell (DC) induction of effective tumor-specific cellular immunity. Pathogen engagement of DC lectins and toll-like receptors (TLRs) shapes immunity by directing T cell function. Strategies to activate specific DC signaling pathways via targeted receptor engagement are crucial to unlocking type 1 cellular immunity. Here, we engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity . VLPs encapsulating TLR7 agonists and decorated with a selective mannose-derived ligand for the lectin DC-SIGN induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand failed to promote DC-mediated immunity. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4 and CD8 T cells that infiltrated solid tumors, inhibiting tumor growth in a murine melanoma model. Thus, VLPs employing lectin-driven immune reprogramming provide a framework for advancing cancer immunotherapies.
缺乏指导树突状细胞(DC)诱导有效肿瘤特异性细胞免疫的策略阻碍了癌症疫苗的开发。病原体与DC凝集素和Toll样受体(TLR)的结合通过指导T细胞功能来塑造免疫。通过靶向受体结合激活特定DC信号通路的策略对于开启1型细胞免疫至关重要。在此,我们设计了一种糖基化病毒样颗粒(VLP)疫苗,该疫苗递送可编程肽抗原以诱导肿瘤特异性细胞免疫。包裹TLR7激动剂并装饰有针对凝集素DC-SIGN的选择性甘露糖衍生配体的VLP可诱导强大的DC激活和1型细胞免疫,而缺乏这种关键DC-SIGN配体的VLP未能促进DC介导的免疫。用糖基化VLP疫苗接种可产生肿瘤抗原特异性的Th1 CD4和CD8 T细胞,这些细胞浸润实体瘤,在小鼠黑色素瘤模型中抑制肿瘤生长。因此,采用凝集素驱动免疫重编程的VLP为推进癌症免疫疗法提供了一个框架。