|Table of Contents|

Construction of a Colon Cancer Tumor Vaccine Targeting Dendritic Cells(PDF)

《南京师大学报(自然科学版)》[ISSN:1001-4616/CN:32-1239/N]

Issue:
2020年03期
Page:
112-119
Research Field:
·生物学·
Publishing date:

Info

Title:
Construction of a Colon Cancer Tumor Vaccine Targeting Dendritic Cells
Author(s):
Song ZhengwenZhao Zhihui
School of Life Sciences,Nanjing Normal University,Institute of Biochemistry and Biological Products,Jiangsu Key Laboratory for Molecular and Medical Biotechnology,Nanjing 210023,China
Keywords:
dendritic cellscolon cancertumor vaccinestreptavidinbiotin
PACS:
Q513
DOI:
10.3969/j.issn.1001-4616.2020.03.018
Abstract:
At present,the issues of predication difficulty for tumor specificity antigens and the ability of these new antigens to be effectively taken up by antigen presenting cells have not been resolved,hence the expected clinical treatment of tumor vaccines has not been achieved,meanwhile,the highly sialylated modification of tumor cell antigens can induce a suppressive immune response in the body. Therefore,this study attempted to use the almost irreversible non-covalent binding principle between Streptavidin(SA)and biotin to cross-link the biotin to the sialic acid modification site of the tumor cell antigen and then to cross-link it with the ligands that bind the activated endocytic receptors of SA to prepare the tumor vaccine. Firstly,the recombinant protein SA-mIgG1Fc that targets dendritic cells(DCs)was constructed and expressed. Secondly,azide-modified unnatural sugars labelled CT26.WT colon cancer cell antigen glycosylation sites via metabolic incorporation pathway,then the biotinylated broad-spectrum tumor antigen(Biotin-TAg)was obtained by covalently conjugating biotin with the azide modification site of the tumor antigen using a biological orthogonal reaction. Finally,the colon cancer tumor vaccine was obtaiend by cross-linking SA-mIgG1Fc with Biotin-TAg at an optimal cross-linked ratio,and the specific antigen contained in which was detected. The results showed that the SA-mIgG1Fc was successfully expressed using genetic engineering methods,and Biotin-TAg capable of binding to SA was obtained,the targeted and stable colon cancer tumor vaccine was prepared by cross-linking SA-mIgG1Fc with Biotin-TAg at an optimal cross-linked mass ratio of 1:48,at the same time,the expression of the specific antigen insulin growth factor-1 receptor(IGF-1R)in the prepared tumor vaccine was detected. This study laid a foundation for the development of a novel tumor vaccine based on methodology.

References:

[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA:a cancer journal for clinicians,2018,68(6):394-424.
[2]CHEN W,ZHENG R,BAADE P D,et al. Cancer statistics in China,2015[J]. CA:a cancer journal for clinicians,2016,66(2):115-132.
[3]FENG R M,ZONG Y N,CAO S M,et al. Current cancer situation in China:good or bad news from the 2018 Global Cancer Statistics?[J]. Cancer communications,2019,39(1):22.
[4]YAGHOUBI N,SOLTANI A,GHAZVINI K,et al. PD-1/PD-L1 blockade as a novel treatment for colorectal cancer[J]. Biomedicine & pharmacotherapy,2019,110:312-318.
[5]XIAO Y,FREEMAN G J. The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy[J]. Cancer discovery,2015,5(1):16-18.
[6]GUAN Q,MA Y,HILLMAN C L,et al. Development of recombinant vaccines against IL-12/IL-23 p40 and in vivo uation of their effects in the downregulation of intestinal inflammation in murine colitis[J]. Vaccine,2009,27(50):7096-7104.
[7]HANZEL J,D’HAENS G R. Anti-interleukin-23 agents for the treatment of ulcerative colitis[J]. Expert opinion on biological therapy,2019:1-8.
[8]BENVENUTI F. The dendritic cell synapse:a life dedicated to T cell activation[J]. Frontiers in immunology,2016,7:1-5.
[9]KADOWAKI N. Dendritic cells:a conductor of T cell differentiation[J]. Allergology international:official journal of the Japanese Society of Allergology,2007,56(3):193-199.
[10]SIEGEL R L,MILLER K D,JEMAL A. Cancer statistics,2018[J]. CA:A cancer journal for clinicians,2018,68(1):7-30.
[11]GIL M,BIENIASZ M,WIERZBICKI A,et al. Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic cells to prime specific CD8+T cell responses in tumor-bearing mice[J]. Journal of immunology,2009,183(10):6808-6818.
[12]SEDLIK C,ORBACH D,VERON P,et al. A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation[J]. Journal of immunology,2003,170(2):846-852.
[13]BOURNAZOS S,RAVETCH J V. Diversification of IgG effector functions[J]. International immunology,2017,29(7):303-310.
[14]CZECH B,HANNON G J. Small RNA sorting:matchmaking for argonautes[J]. Nature reviews genetics,2011,12(1):19-31.
[15]PERDICCHIO M,ILARREGUI J M,VERSTEGE M I,et al. Sialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells[J]. Proceedings of the national academy of sciences of the United States of America,2016,113(12):3329-3334.
[16]CHEN W,ZHENG R,BAADE P D,et al. Cancer statistics in China,2015[J]. CA:A cancer journal for clinicians,2016,66(2):115-132.
[17]BAI L,HU Z,WANG F,et al. Generation of streptavidin-tagged human-granulocyte macrophage colony-stimulating factor fusion proteins[J]. Journal of Southern Medical University,2012,32(10):1389-1393.
[18]NING X,GUO J,WOLFERT M A,et al. Visualizing metabolically labeled glycoconjugates of living cells by copper-free and fast huisgen cycloadditions[J]. Angewandte chemie,2008,47(12):2253-2255.
[19]SANO T,CANTOR C R. Streptavidin-containing chimeric proteins:design and production[J]. Methods in enzymology,2000,326:305-311.
[20]KAWAMATA T,TOMARI Y. Making RISC[J]. Trends in biochemical sciences,2010,35(7):368-376.
[21]NAKAMURA M,MIE M,FUNABASHI H,et al. Construction of streptavidin-luciferase fusion protein for ATP sensing with fixed form[J]. Biotechnology letters,2004,26(13):1061-1066.
[22]SABADO R L,BALAN S,BHARDWAJ N. Dendritic cell-based immunotherapy[J]. Cell research,2017,27(1):74-95.
[23]SHINDE P,MELINKERI S,SANTRA M K,et al. Autologous hematopoietic stem cells are a preferred source to generate dendritic cells for immunotherapy in multiple myeloma patients[J]. Frontiers in immunology,2019,10:1079.
[24]DRAUBE A,KLEIN G N,MATTHEUS S,et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer:a systematic review and meta-analysis[J]. PloS one,2011,6(4):e18801.
[25]PHAM G H,IGLESIAS B V,GOSSELIN E J. Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading,vaccination,and protection using intranasally administered antigen-pulsed dendritic cells[J]. Vaccine,2014,32(40):5212-5220.

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Last Update: 2020-09-15