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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2023 01

Page:

24-32

Research Field:

Publishing date:

Info

Title:

Preparation and evaluation of neutrophil-loaded neoantigen peptide and CD73 inhibitor nanoparticles vaccine on gastric cancer

Author(s):

ZHAI Qingqing¹; CHU Yanhong²; QIN Lanqun²; ZHANG Xiaoli²; ZHOU Xipeng²; LIU Qin²; LIU Baorui¹

1.The Comprehensive Cancer Centre,Nanjing Drum Tower Hospital,Clinical College of Nanjing Medical University,Jiangsu Nanjing 210008,China;2.the Comprehensive Cancer Centre,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Jiangsu Nanjing 210008,China.

Keywords:

gastric cancer; MFC cells; neoantigen peptide; neutrophil; vaccine; CD73 inhibitor; nanoparticles

PACS:

R735.2

DOI:

10.3969/j.issn.1672-4992.2023.01.004

Abstract:

Objective:To prepare and characterize neutrophils (NEs)-loaded neoantigen peptide and CD73 inhibitor nanoparticles (NPs) vaccine,and to preliminarily evaluate its antitumor effect in gastric tumor-bearing 615 mice.Methods:NEs mouse bone marrow derived NEs were isolated and purified by Percoll gradient density centrifugation.The gastric cancer cells MFC derived neoantigen peptide were linked with DSPE-PEG2000 (DP-MFC) and the CD73 inhibitor NPs (antiCD73) were prepared by phacoemulsification and solvent evaporation technology.The vaccine was prepared by co-incubating the NEs with DP-MFC and adjuvant (DP-MFC-NEs vaccine) or both DP-MFC and antiCD73NPs with adjuvant (combined vaccine).The therapeutic effect of the vaccines on gastric cancer was observed in tumor-bearing 615 mice.Results:About 1.5¡Á106 NEs could be isolated and purified from a 10-week-old 615 mouse.The cell activity and purity were above 95% and 90% respectively.Compared with control mice,the growth of subcutaneous tumor in mice treated with DP-MFC-NEs vaccine was significantly inhibited,and some of them were cured (CR).The proportions of CD4+ and CD8+ cells in their lymph nodes were significantly higher (P<0.05).Those CR mice were subcutaneously inoculated with MFC cells again,and no tumor recurred.Mice treated with the combined vaccine had the highest survival rate (75%,P=0.038).Conclusion:Neutrophil vaccine loaded with neoantigen peptides derived from gastric cancer cells and CD73 inhibitor NPs has no obvious toxicity to mice,and can inhibit tumor growth and even cure mice.The vaccine could activate a memory-type immune response in mice.

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