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作者:

Liang, Zhaoyuan (Liang, Zhaoyuan.) | Cui, Xinyue (Cui, Xinyue.) | Yang, Liqun (Yang, Liqun.) | Hu, Qin (Hu, Qin.) | Li, Danyang (Li, Danyang.) | Zhang, Xiaofei (Zhang, Xiaofei.) | Han, Lu (Han, Lu.) | Shi, Siwei (Shi, Siwei.) | Shen, Yurong (Shen, Yurong.) | Zhao, Weijian (Zhao, Weijian.) | Ju, Qi (Ju, Qi.) | Deng, Xiongwei (Deng, Xiongwei.) | Wu, Yan (Wu, Yan.) | Sheng, Wang (Sheng, Wang.) (学者:盛望)

收录:

SCIE

摘要:

Cancer vaccines targeting tumor specific neoantigens derived from nonsynonymous mutations of tumor cells have emerged as an effective approach to induce antitumor T cells responses for personalized cancer immunotherapy. Despite the enormous potential of synthetic peptides as a common modality for neoantigen vaccines, their practical efficacy was limited due to their relatively low immunogenicity. Herein, we modify neoantigen peptide (Adpgk) derived from MC-38 colon carcinoma by supplementing ten consecutive positively-charged lysines (10 K-Adpgk) to obtain cationic polypeptide. And then we made them self-assemble with toll-like receptor 9 (TLR-9) agonist CpG oligodeoxynucleotides (CpG ODN) adjuvant directly forming antigen/adjuvant integrated nanocomplexes (PCNPs) through electrostatic interaction for potent tumor immunotherapy. The optimal formed PCNPs were around 175 nm with uniform size distribution and could maintain stability in physiological saline solution. CpG ODN and 10 K-Adpgk in the formed PCNPs could be effectively uptake by dendritic cells (DCs) and stimulate the maturation of DCs as well as improving the efficiency of antigen crosspresentation efficiency in vitro. Furthermore, the PCNPs vaccine could markedly improve neoantigen and adjuvant co-delivery efficiency to lymphoid organs and activate cytotoxic T cells. In addition, vaccination with PCNPs could not only offer prophylactic to protect mice from challenged MC-38 colorectal tumors, but also achieve a better anti-tumor effect in an established colorectal tumor model, and significantly prolong the survival rate of tumor-bearing mice. Therefore, this work provided a versatile but effective method for neoantigen peptide and CpG ODN co-assembly vaccine platform for efficient colorectal cancer immunotherapy.

关键词:

CpG ODN Immunotherapy Nanovaccine Neoantigen Peptide

作者机构:

  • [ 1 ] [Liang, Zhaoyuan]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 2 ] [Cui, Xinyue]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 3 ] [Yang, Liqun]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 4 ] [Hu, Qin]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 5 ] [Li, Danyang]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 6 ] [Zhang, Xiaofei]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 7 ] [Han, Lu]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 8 ] [Shi, Siwei]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 9 ] [Shen, Yurong]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 10 ] [Zhao, Weijian]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 11 ] [Ju, Qi]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 12 ] [Sheng, Wang]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 13 ] [Deng, Xiongwei]Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China
  • [ 14 ] [Wu, Yan]Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China

通讯作者信息:

  • 盛望

    [Sheng, Wang]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China;;[Deng, Xiongwei]Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China;;[Wu, Yan]Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China

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来源 :

INTERNATIONAL JOURNAL OF PHARMACEUTICS

ISSN: 0378-5173

年份: 2021

卷: 608

5 . 8 0 0

JCR@2022

ESI学科: PHARMACOLOGY & TOXICOLOGY;

ESI高被引阀值:6

被引次数:

WoS核心集被引频次: 8

SCOPUS被引频次: 10

ESI高被引论文在榜: 0 展开所有

万方被引频次:

中文被引频次:

近30日浏览量: 2

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