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
一种基于纳米抗体的新型 CTLA-4 阻断策略增强了树突状细胞疫苗刺激的抗肿瘤细胞毒性 T 淋巴细胞的活性
英文原题：A novel CTLA-4 blocking strategy based on nanobody enhances the activity of dendritic cell vaccine-stimulated antitumor cytotoxic T lymphocytes.
查看英文原题
A novel CTLA-4 blocking strategy based on nanobody enhances the activity of dendritic cell vaccine-stimulated antitumor cytotoxic T lymphocytes.
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中文摘要
尽管CTLA-4阻断在癌症治疗中取得了巨大成功，但抗CTLA-4单克隆抗体的使用仍面临许多局限性。如今，免疫检查点阻断联合过继细胞疗法正受到广泛关注。在本文中，我们报道了一种基于抗CTLA-4纳米抗体（Nb）修饰脂质体的策略来改善这些障碍。
我们构建了Nb36/脂质体复合物，并将其用作CTLA-4/B7信号通路的阻断剂，与树突状细胞（DC）/肿瘤融合疫苗联合使用，以增强CD8+ T细胞细胞因子分泌、活化、增殖以及特异性细胞毒性。
此外，由LPS-Nb36和DC/肿瘤融合疫苗诱导的CD8+ T细胞在体内产生了更高的CD8+ T细胞效应功能，显著延缓了荷瘤小鼠（HepG2、A549和MGC-803）的肿瘤生长并延长了其生存期。
我们的数据表明，抗CTLA-4 Nb修饰脂质体与DC/肿瘤融合疫苗联合使用，在体外和体内均增强了CD8+ T细胞的抗肿瘤活性，有望成为T细胞功能障碍或对抗CTLA-4 mAb治疗不佳的恶性肿瘤患者的替代疗法。
展开英文摘要原文
Despite the great success of CTLA-4 blocking in cancer treatment, the use of anti-CTLA-4 monoclonal antibodies still faces many limitations. Now, immune checkpoint blocking coupled with adoptive cell therapy is gaining much attention. In this paper, we reported a strategy on the basis of anti-CTLA-4 nanobody (Nb)-modified liposomes to improve these obstacles.
An Nb36/liposome complex was constructed and utilized as a blocker of the CTLA-4/B7 signal pathway in a combination with dendritic cell (DC)/tumor fusion vaccine to enhance the CD8 + T cell cytokine secretion, activation, proliferation, as well as specific cytotoxicity.
Moreover, the CD8 + T cells induced by LPS-Nb36 and DC/tumor fusion vaccine led to higher CD8 + T cell effector function in vivo, which significantly retarded tumor growth and lengthened survival of tumor-bearing mice (HepG2, A549, and MGC-803).
Our data demonstrate that the anti-CTLA-4 Nb-modified liposomes in connection with DC/tumor fusion vaccines enhance the CD8 + T cell antitumor activity in vitro and in vivo, and is expected to be an alternative therapy for patients with malignancies that have T cell dysfunction or have poor treatment against anti-CTLA-4 mAb.
论文信息
- 作者
- Yang W、Pang Y、Wang X、Lai Z、Lu Y、Zheng S、Wang W
- 第一作者单位
- Public Research Center of Hainan Medical University, Hainan Medical University, Haikou, 570100, China.China
- 通讯作者单位
- Public Research Center of Hainan Medical University, Hainan Medical University, Haikou, 570100, China. wangwu19880406@sina.com.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell death & disease2023 Jul 7
- 原文标识
- PubMed 37419930 · DOI 10.1038/s41419-023-05914-w
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