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摘要: 免疫治疗是当前最受关注的肿瘤治疗方式之一，免疫检查点抑制剂、细胞治疗和肿瘤疫苗等免疫治疗手段，在临床上取得了重要进展。近年来，除了以单抗药物为代表的免疫检查点抑制剂以外，多肽药物也逐渐受到关注。本文着重总结多肽药物在免疫检查点抑制剂方面的研究进展及应用，包括单靶点多肽阻断剂、双功能多肽阻断剂、自组装多肽，以及免疫检查点多肽在肿瘤诊断中的应用等，并对多肽药物目前面临的瓶颈问题提出思考，为多肽药物在肿瘤免疫治疗中的应用提供新的思路。
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关键词:
- 肿瘤 /
- 免疫治疗 /
- 多肽药物 免疫检查点
Abstract: Immunotherapy has emerged as the most widely used cancer treatment strategy. Immune checkpoint blockade, cell therapy, and tumor vaccines have all achieved remarkable progress in clinical trials. Over recent years, monoclonal antibodies and peptide drugs have gained increasing attention as representatives for immune checkpoint blockades. This review summarized the research progress and application of peptide drugs targeting immune checkpoints, including single-target peptide blockers, bifunctional peptide blockers, and self-assembled peptides, as well as the application of peptides targeting immune checkpoints in cancer diagnosis. In addition, we offer new ideas to the bottleneck faced by peptide drugs for application in cancer immunotherapy.-
Key words:
- cancer, immunotherapy /
- peptide drugs /
- immune checkpoint
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表 1 免疫检查点多肽阻断剂
靶点 多肽 氨基酸序列 类型 功能 PD-1 P-F4 FSGTVTTAGLLF L肽 P-F4-NPs纳米粒子瘤内给药显著抑制CT26荷瘤模型的肿瘤生长 C8 CKWYRPSEC 环肽 抑制CT26、B16-OVA以及B16荷瘤模型的肿瘤
生长PD-L1 CLP-002 WHRSYYTWNLNT L肽 抑制CT26荷瘤模型的肿瘤生长 TPP-1 YASYHCWCWRDPGRS L肽 具有激活T细胞杀伤肿瘤的作用 SPAM MPIFLDHILNKFWILHYA L肽 选择性高亲和hPD-L1 Pep1 CLQKTPKQC 环肽 与PD-L1结合力为373 nM，显著抑制CT26荷瘤模型的肿瘤生长 Pep2 CVRARTR L肽 与PD-L1结合力为281 nM，相较于pep1，pep2的抑瘤效果更为显著 DPPA-1 NYSKPTDRQYHF D肽 首个PD-1/PD-L1抗酶解的D肽阻断剂，显著抑制CT26荷瘤模型的肿瘤生长 OPBP-1 GQSEHHMRVYSF D肽 首个报道的可口服的肿瘤免疫检查点多肽阻断剂，经TMC包裹口服生物利用度显著提高 NP-12 
分枝肽 显著抑制CT26和B16F10荷瘤模型的肿瘤生长，与化疗联合能够协同增强抗肿瘤效果 MOPD-1 IQIREYKRCGQDEERVRRECKERGERQNCHYVIHKEGNCYVCGIICL 环肽 抵抗酶降解，显著抑制CT26荷瘤模型的肿瘤生长 TIGIT DTBP-3 GGYTFHWHRLNP D肽 首个TIGIT抗酶解的D肽阻断剂，已被用于临床PET-CT LAG-3 C25 CVPMTYRAC 环肽 显著抑制CT26、B16和B16-OVA荷瘤模型的肿瘤生长 CD47 pep-20-D12 awsATWSNYwrh D构型氨基酸
保护肽显著抑制MC38和B16-OVA荷瘤模型的肿瘤生长，与放疗联用具有显著的协同效果 SIRPα D4-2 YRYSAVYSIHPSWCG 环肽 协同增强利妥昔单抗抑制Raji荷瘤模型的肿瘤生长，与gp75抗体联用能够减少B16BL6荷瘤模型的肺转移 
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