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
一种淋巴结靶向的细胞-纳米佐剂偶联物增强树突状细胞与 T 细胞的相互作用用于癌症免疫治疗
英文原题：A lymph node-targeted cell-nanoadjuvant conjugate enhances dendritic cell-T cell crosstalk for cancer immunotherapy.
查看英文原题
A lymph node-targeted cell-nanoadjuvant conjugate enhances dendritic cell-T cell crosstalk for cancer immunotherapy.
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中文摘要
树突状细胞（DC）疫苗通过激发强效抗肿瘤免疫，代表了一种有前景的免疫治疗策略。然而，由于其淋巴结（LN）靶向性差和T细胞激活不足，其临床应用仍然受限。在此，我们通过点击化学将抗PD-1抗体（αPD-1）和Resiquimod（R848）脂质体偶联至DC疫苗（DCVs）上，开发了一种LN靶向的细胞-纳米佐剂偶联物（DCV-αPD-1/Lipo），以增强DC-T细胞串扰用于癌症免疫治疗。DCV-αPD-1/Lipo维持了更高的共刺激分子表达和抗原呈递，并具有优于传统DC疫苗的LN靶向效率。表面偶联的αPD-1使DC-T细胞黏附增加4.97倍，同时放大IFN-γ/IL-12正反馈环路，从而增强T细胞活性并增强效应T细胞及其他免疫细胞介导的抗肿瘤疗效。这种适应性DC治疗、纳米佐剂和检查点阻断的多功能整合为下一代DC治疗建立了一种有效方法。
展开英文摘要原文
Dendritic cell (DC) vaccines represent a promising immunotherapeutic strategy by eliciting potent anti-tumor immunity.
However, their clinical application remains limited due to poor lymph node (LN) targeting and inadequate T cell activation.
Here, we developed an LN-targeted cell-nanoadjuvant conjugate by click-chemistry conjugation of anti-PD-1 antibodies ( α PD-1) and Resiquimod (R848) liposomes to DC vaccines (DCVs) (DCV- α PD-1/Lipo) to enhance DC-T cell crosstalk for cancer immunotherapy. DCV- α PD-1/Lipo maintains higher co-stimulatory molecule expression and antigen presentation with enhanced LN targeting efficiency than conventional DC vaccines.
The surface-conjugated α PD-1 increases DC-T cell adhesion by 4. 97-fold while amplifying the IFN- γ /IL-12 positive feedback loop, thereby potentiating T cell activity and augmenting effector T cells and other immune cells mediated anti-tumor efficacy. This multifunctional integration of adaptive DC therapy, nanoadjuvants and checkpoint blockade establishes an effective approach for next-generation DC therapy.
论文信息
- 作者
- Hu S、Yi W、Zhao Z、Qian X、Jiang L、Cao Y、Yan D、Teng L
- 第一作者单位
- School of Life Sciences, Jilin University, Changchun 130012, China.China
- 通讯作者单位
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.China
- 期刊
- Acta pharmaceutica Sinica. B2026 Jun
- 原文标识
- PubMed 42368580 · DOI 10.1016/j.apsb.2025.12.032