PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
髓系细胞触发的原位细胞工程用于稳健的疫苗型癌症治疗
英文原题：Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.
查看英文原题
Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.
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中文摘要
继树突状细胞（DC）疫苗取得成功之后，基于细胞的肿瘤疫苗显示出其作为一种疫苗接种策略的前景。除DC细胞外，靶向其他免疫细胞，尤其是髓系细胞，有望解决目前尚未满足的临床需求（例如肿瘤类型、细胞因子风暴等安全性问题以及治疗获益）。在此，研究表明，原位注射的大孔髓系细胞过继支架（MAS）不仅能主动递送由支架浸润细胞表面硫醇基团触发的抗原（Ags），还能释放粒细胞-巨噬细胞集落刺激因子及其他佐剂组合。因此，这促进了所产生的单核细胞和DC疫苗（MASVax）的细胞分化、活化和迁移，从而激发抗肿瘤T细胞免疫。基于新抗原的MASVax联合免疫检查点阻断可诱导已建立肿瘤的排斥和长期免疫保护。联合清除免疫抑制性髓系细胞进一步增强了MASVax的疗效，表明基于髓系细胞的疗法在癌症免疫增强和正常化治疗方面具有潜力。
展开英文摘要原文
Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e. g. , tumor types, safety issues such as cytokine storms, and therapeutic benefits).
Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity.
Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.
论文信息
- 作者
- Li WH、Su JY、Zhang BD、Zhao L、Zhuo SH、Wang TY、Hu HG、Li YM
- 单位
- Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.China
- 期刊
- Advanced materials (Deerfield Beach, Fla.)2024 Apr
- 原文标识
- PubMed 38295870 · DOI 10.1002/adma.202308155