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
生成 CD137L-DC-EBV-VAX 抗癌疫苗的方法
英文原题：Methods for generating the CD137L-DC-EBV-VAX anti-cancer vaccine.
查看英文原题
Methods for generating the CD137L-DC-EBV-VAX anti-cancer vaccine.
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中文摘要
树突状细胞（DC）是专业的抗原提呈细胞（APC），能够高效地将捕获的抗原提呈给细胞毒性T细胞，并启动强大的抗原特异性反应。因此，DC已被探索用于癌症免疫治疗。然而，由于外周血中DC数量稀少，使用前需要体外扩增以产生足够的DC。大多数基于DC的肿瘤疫苗利用由GM-CSF和IL-4生成的单核细胞衍生DC（mo-DC）。在此，我们描述了一种新型DC——CD137L-DC的生成，其通过CD137配体激动剂刺激单核细胞而产生，并证明在体外诱导针对肿瘤相关病毒（如EBV和HBV）的细胞毒性反应方面比经典mo-DC更有效。在一项针对局部复发或转移性NPC患者的I期临床试验中，CD137L-DC-EBV疫苗显示出良好的耐受性和延长的患者生存期，为进一步开发CD137L-DC疫苗用于免疫治疗提供了基础。
展开英文摘要原文
Dendritic cells (DC) are professional antigen presenting cells (APCs) that can efficiently present captured antigens to cytotoxic T cells and initiate powerful antigen-specific responses.
Therefore, DC have been explored for cancer immunotherapy. However, due to the scarcity of DCs in the peripheral blood, ex-vivo expansion is required to generate sufficient DCs before use. The majority of DC-based tumor vaccines utilize monocyte-derived DC (mo-DC) that are generated with GM-CSF and IL-4.
Here, we describe the generation of a novel type of DC, CD137L-DC, which are generated from monocytes by stimulation with a CD137 ligand agonist, and that proved to be more potent than classical mo-DC in inducing cytotoxic responses against tumor associated viruses, such as EBV and HBV in vitro. In a phase I clinical trial on patients with locally recurrent or metastatic NPC, a CD137L-DC-EBV vaccine showed good tolerability and prolonged patient survival, providing a basis for further development of CD137L-DC vaccines for immunotherapy.
论文信息
- 作者
- Nickles E、Xia R、Sun R、Schwarz H
- 第一作者单位
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.Singapore
- 通讯作者单位
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, Singapore, Singapore. Electronic address: phssh@nus.edu.sg.Singapore
- 期刊
- Methods in cell biology2024
- 原文标识
- PubMed 38548412 · DOI 10.1016/bs.mcb.2023.07.002