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细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性

邵世帅, 段树康, 田浤, 姚文兵, 高向东

邵世帅, 段树康, 田浤, 姚文兵, 高向东. 细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性[J]. 中国药科大学学报, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803
引用本文: 邵世帅, 段树康, 田浤, 姚文兵, 高向东. 细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性[J]. 中国药科大学学报, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803
SHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine[J]. Journal of China Pharmaceutical University, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803
Citation: SHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine[J]. Journal of China Pharmaceutical University, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803

细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性

基金项目: 国家自然科学基金资助项目(No.82073754,No.81973222);新疆维吾尔自治区重点研发计划(No.2020B03003)

Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine

Funds: This study was supported by the National Natural Science Foundation of China (No.82073754, No.81973222); and the Key Research and Development Program of Xinjiang Uygur Autonomous Region (No.2020B03003)
  • 摘要: 目前已有多款细胞程序性死亡受体1(PD-1)和其配体(PD-L1)免疫检查点阻断抗体用于临床治疗,但只有部分患者表现出临床反应,因此需要一种替代的肿瘤免疫治疗策略。以PD-L1为靶点的治疗性肿瘤疫苗是一种有意义的尝试。本研究设计了以PD-L1为靶点的表位肽疫苗,然后基于人源化免疫系统(HIS)小鼠模型筛选,具有免疫原性的PD-L1表位肽,进一步研究其抗肿瘤活性。结果显示,设计并筛选得到的PD-L1-B1表位肽疫苗不仅成功诱导了PD-L1特异性的体液免疫和细胞免疫,还表现出抗肿瘤活性。此外,免疫治疗还增加了肿瘤的T淋巴细胞浸润,重塑了肿瘤免疫抑制微环境。综上所述,PD-L1-B1表位肽疫苗表现出强效的抗肿瘤活性,对PD-1/PD-L1阻断不敏感的患者可能是一种有效的替代免疫治疗策略。
    Abstract: Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immunogenic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addition, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.
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出版历程
  • 收稿日期:  2023-02-27
  • 修回日期:  2023-04-02
  • 刊出日期:  2023-04-24

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