• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

联合 VEGFR 肽药物偶联物和抗 PD-1 抗体治疗肝细胞癌的疗效增强。

Enhanced efficacy of combined VEGFR peptide-drug conjugate and anti-PD-1 antibody in treating hepatocellular carcinoma.

机构信息

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.

出版信息

Sci Rep. 2024 Sep 17;14(1):21728. doi: 10.1038/s41598-024-72907-w.

DOI:10.1038/s41598-024-72907-w
PMID:39289512
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408695/
Abstract

This study aimed to design a VEGFR-targeting peptide-drug conjugate with the ability to decrease tumor burden and suppress tumor angiogenesis, and to further evaluate the therapeutic effect of anti-PD-1 antibody in HCC therapy. A VEGFR-targeting peptide VEGF (QR) was conjugated with a lytic peptide (KLU) to form a peptide-drug conjugate QR-KLU. And the efficacy of QR-KLU in combination with anti-PD-1 antibody for HCC therapy in vivo and in vitro were evaluated. QR-KLU inhibited the proliferation and migration of mouse HCC cell line (Hepa1-6) cells under normoxic and hypoxic conditions in a dose-dependent manner. In the subcutaneous Hepa1-6 tumor model, QR-KLU combined with the anti-PD-1 antibody substantially inhibited tumor growth, promoted tumor necrosis, and prolonged the survival time of tumor-bearing mice. QR-KLU substantially inhibited hypoxia-induced expression of VEGF, promoted tumor vascular normalization, and increased cluster of differentiation 8 (CD8) T cell infiltration in the tumor. In addition, QR-KLU and anti-PD-1 antibody demonstrated a strong synergistic effect in promoting the activation of intratumoral CD8 T cells, reducing the expression of immune-inhibitory factors, and increasing the expression of immune-stimulatory factors. This study proposed a novel approach for enhancing the efficacy of anti-PD-1 antibody using a VEGFR-targeting peptide-drug conjugate in HCC therapy.

摘要

这项研究旨在设计一种具有降低肿瘤负担和抑制肿瘤血管生成能力的 VEGFR 靶向肽药物偶联物，并进一步评估抗 PD-1 抗体在 HCC 治疗中的治疗效果。将 VEGFR 靶向肽 VEGF（QR）与溶瘤肽（KLU）连接形成肽药物偶联物 QR-KLU。并评估了 QR-KLU 与抗 PD-1 抗体联合用于 HCC 体内和体外治疗的疗效。QR-KLU 可在常氧和缺氧条件下以剂量依赖性方式抑制小鼠 HCC 细胞系（Hepa1-6）细胞的增殖和迁移。在皮下 Hepa1-6 肿瘤模型中，QR-KLU 与抗 PD-1 抗体联合可显著抑制肿瘤生长，促进肿瘤坏死，并延长荷瘤小鼠的生存时间。QR-KLU 可显著抑制缺氧诱导的 VEGF 表达，促进肿瘤血管正常化，并增加肿瘤内 CD8 T 细胞浸润。此外，QR-KLU 和抗 PD-1 抗体在促进肿瘤内 CD8 T 细胞激活、降低免疫抑制因子表达和增加免疫刺激因子表达方面表现出很强的协同作用。这项研究提出了一种使用 VEGFR 靶向肽药物偶联物增强抗 PD-1 抗体在 HCC 治疗中的疗效的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/2ab2b5831103/41598_2024_72907_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/713b5ef23e60/41598_2024_72907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/9eb06798dc80/41598_2024_72907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/df87232a4d64/41598_2024_72907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/d3ed29dc1890/41598_2024_72907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/d46270d71bbd/41598_2024_72907_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/5e6337ea08c3/41598_2024_72907_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/9b1227f3e498/41598_2024_72907_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/2ab2b5831103/41598_2024_72907_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/713b5ef23e60/41598_2024_72907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/9eb06798dc80/41598_2024_72907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/df87232a4d64/41598_2024_72907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/d3ed29dc1890/41598_2024_72907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/d46270d71bbd/41598_2024_72907_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/5e6337ea08c3/41598_2024_72907_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/9b1227f3e498/41598_2024_72907_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e996/11408695/2ab2b5831103/41598_2024_72907_Fig8_HTML.jpg

相似文献

1
Enhanced efficacy of combined VEGFR peptide-drug conjugate and anti-PD-1 antibody in treating hepatocellular carcinoma.联合 VEGFR 肽药物偶联物和抗 PD-1 抗体治疗肝细胞癌的疗效增强。
Sci Rep. 2024 Sep 17;14(1):21728. doi: 10.1038/s41598-024-72907-w.
2
Dual Programmed Death Receptor-1 and Vascular Endothelial Growth Factor Receptor-2 Blockade Promotes Vascular Normalization and Enhances Antitumor Immune Responses in Hepatocellular Carcinoma.双重程序性死亡受体 1 和血管内皮生长因子受体 2 阻断促进肝癌血管正常化并增强抗肿瘤免疫反应。
Hepatology. 2020 Apr;71(4):1247-1261. doi: 10.1002/hep.30889. Epub 2019 Oct 14.
3
Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101.Combretastatin A4 纳米粒和 DC101 增强依赖肿瘤血管破坏和正常化的抗 PD-1 疗法治疗肝细胞癌
Theranostics. 2021 Apr 3;11(12):5955-5969. doi: 10.7150/thno.58164. eCollection 2021.
4
Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model.仑伐替尼的免疫调节活性有助于 Hepa1-6 肝癌模型的抗肿瘤活性。
Cancer Sci. 2018 Dec;109(12):3993-4002. doi: 10.1111/cas.13806. Epub 2018 Nov 16.
5
Molecular targeting of VEGF/VEGFR signaling by the anti-VEGF monoclonal antibody BD0801 inhibits the growth and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo.抗VEGF单克隆抗体BD0801对VEGF/VEGFR信号通路的分子靶向作用在体外和体内均能抑制人肝癌细胞的生长并诱导其凋亡。
Cancer Biol Ther. 2017 Mar 4;18(3):166-176. doi: 10.1080/15384047.2017.1282019. Epub 2017 Feb 10.
6
Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma.姜黄素与抗程序性细胞死亡蛋白-1 在肝细胞癌中的协同疗效。
Life Sci. 2021 Aug 15;279:119359. doi: 10.1016/j.lfs.2021.119359. Epub 2021 Mar 19.
7
Disruption of SIRT7 Increases the Efficacy of Checkpoint Inhibitor via MEF2D Regulation of Programmed Cell Death 1 Ligand 1 in Hepatocellular Carcinoma Cells.SIRT7 缺失通过 MEF2D 调控程序性细胞死亡配体 1 增加肝癌细胞中检查点抑制剂的疗效。
Gastroenterology. 2020 Feb;158(3):664-678.e24. doi: 10.1053/j.gastro.2019.10.025. Epub 2019 Oct 31.
8
Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma.regorafenib 联合 PD1 阻断通过诱导肝细胞癌中 CXCL10 的表达增加 CD8 T 细胞浸润。
J Immunother Cancer. 2020 Nov;8(2). doi: 10.1136/jitc-2020-001435.
9
Antiangiogenic and Antitumor Activities of Aflibercept, a Soluble VEGF Receptor-1 and -2, in a Mouse Model of Hepatocellular Carcinoma.可溶性血管内皮生长因子受体1和2阿柏西普在肝细胞癌小鼠模型中的抗血管生成和抗肿瘤活性
Neoplasia. 2016 Jul;18(7):413-24. doi: 10.1016/j.neo.2016.05.001.
10
Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma.阿帕替尼靶向肝癌中的肿瘤细胞和内皮细胞。
Cancer Med. 2018 Sep;7(9):4570-4583. doi: 10.1002/cam4.1664. Epub 2018 Aug 14.

引用本文的文献

1
Recent Advances in Augmenting the Therapeutic Efficacy of Peptide-Drug Conjugates.增强肽-药物偶联物治疗效果的最新进展
J Med Chem. 2025 May 8;68(9):9037-9056. doi: 10.1021/acs.jmedchem.5c00007. Epub 2025 Apr 23.
2
Peptides as Versatile Regulators in Cancer Immunotherapy: Recent Advances, Challenges, and Future Prospects.肽作为癌症免疫治疗中的多功能调节剂：最新进展、挑战与未来展望
Pharmaceutics. 2025 Jan 1;17(1):46. doi: 10.3390/pharmaceutics17010046.
3
Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches.

本文引用的文献

1
BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis.BICC1 通过诱导血管生成而促进胰腺癌的进展，与 VEGF 无关。
Signal Transduct Target Ther. 2023 Jul 14;8(1):271. doi: 10.1038/s41392-023-01478-5.
2
Therapeutic blocking of VEGF binding to neuropilin-2 diminishes PD-L1 expression to activate antitumor immunity in prostate cancer.治疗性阻断 VEGF 与神经纤毛蛋白-2 的结合可降低 PD-L1 表达，激活前列腺癌中的抗肿瘤免疫。
Sci Transl Med. 2023 May 3;15(694):eade5855. doi: 10.1126/scitranslmed.ade5855.
3
Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma.
肝细胞癌的新一代免疫疗法：耐药机制与新型治疗方法
Cancers (Basel). 2025 Jan 13;17(2):236. doi: 10.3390/cancers17020236.
穿膜肽修饰的石蒜碱传递体经皮治疗皮肤鳞状细胞癌。
J Nanobiotechnology. 2023 Apr 28;21(1):139. doi: 10.1186/s12951-023-01877-4.
4
Immuno-oncology clinical trials take a turn beyond PD1/PDL1 inhibitors.免疫肿瘤学临床试验超越PD1/PDL1抑制剂，出现新变化。
Nat Rev Drug Discov. 2023 Jun;22(6):442-443. doi: 10.1038/d41573-023-00066-0.
5
Microfluidic formulation of anticancer peptide loaded ZIF-8 nanoparticles for the treatment of breast cancer.载抗癌肽的 ZIF-8 纳米粒子的微流体制备及其用于乳腺癌治疗。
J Colloid Interface Sci. 2023 Jul 15;642:810-819. doi: 10.1016/j.jcis.2023.03.172. Epub 2023 Mar 30.
6
Targeting angiogenesis in oncology, ophthalmology and beyond.针对肿瘤学、眼科及其他领域的血管生成。
Nat Rev Drug Discov. 2023 Jun;22(6):476-495. doi: 10.1038/s41573-023-00671-z. Epub 2023 Apr 11.
7
Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma.靶向 PPAR-γ 可逆转肝癌对免疫检查点阻断的适应性。
Gut. 2023 Sep;72(9):1758-1773. doi: 10.1136/gutjnl-2022-328364. Epub 2023 Apr 5.
8
Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma.外泌体来源的 circCCAR1 促进肝癌中 CD8+T 细胞功能障碍和抗 PD1 耐药性。
Mol Cancer. 2023 Mar 18;22(1):55. doi: 10.1186/s12943-023-01759-1.
9
Anti-Cancer Peptides: Status and Future Prospects.抗癌肽：现状与未来展望。
Molecules. 2023 Jan 23;28(3):1148. doi: 10.3390/molecules28031148.
10
Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers.肝细胞癌：分子机制、靶向治疗和生物标志物。
Cancer Metastasis Rev. 2023 Sep;42(3):629-652. doi: 10.1007/s10555-023-10084-4. Epub 2023 Feb 2.