Effects of hMIP-1beta gene modification on in vivo tumorigenicity and vaccine efficacy of tumor cells.
- Author:
Xiao-Ling LUO
1
;
Yu-An XIE
;
Zhi-Peng KUANG
;
Ji-Ning WU
;
An-Min LIANG
Author Information
- Publication Type:Journal Article
- MeSH: Adenocarcinoma; metabolism; pathology; Adenoviridae; genetics; Animals; CD4-Positive T-Lymphocytes; immunology; CD8-Positive T-Lymphocytes; immunology; Cancer Vaccines; Cell Line, Tumor; Chemokine CCL4; genetics; metabolism; Chemotaxis, Leukocyte; Colonic Neoplasms; metabolism; pathology; Cytotoxicity, Immunologic; Dendritic Cells; immunology; Female; Genetic Vectors; Humans; Killer Cells, Natural; immunology; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Random Allocation; Recombinant Proteins; genetics; metabolism; Transfection; Tumor Burden
- From: Chinese Journal of Oncology 2008;30(2):97-102
- CountryChina
- Language:Chinese
-
Abstract:
UNLABELLEDOBJECTIVE To explore the effects of human macrophage inflammatory protein-1 beta (hMIP-1beta) modification on the in vivo tumorigenicity and vaccine efficacy of tumor cells.
METHODSMurine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus carring the hMIP-1beta gene (AdhMIP-1beta). The efficacy of gene transfection was tested by X-gal staining. The hMIP-1beta level in the supernatant of hMIP-1beta gene-modified CT26 cells was assayed by ELISA, and the chemotactic activity for CD4+ T cells, CD8+ T cells, NK cells and immature dendritic cells (imDCs) were assayed by a transwell chamber. The changes of growth characteristics and in vivo tumorigenicity of hMIP-1beta gene-modified CT26 cells were also assessed. BALB/c mice were immunized with hMIP-1beta gene-modified CT26 tumor vaccine and the antitumor effect was evaluated.
RESULTShMIP-1beta gene could be transfected into CT26 cells by AdhMIP-1beta with an efficiency over 95%. The level of hMIP-1beta in the culture supernatant of hMIP-1beta gene-modified CT26 cells was 980 pg/ml and the supernatant displayed ramarkable chemotactic activity to CD4+ T cells, CD8+ T cells, NK cells and imDCs compared with LacZ gene-modified CT26 cells and control. When the hMIP-1beta gene-modifited CT26 cells were subcutaneously inoculated in BALB/c mice, the tumorigencity was delayed and suppressed, and overt necrosis and lymphocyte infiltration were observed in the tumor tissue, but not in those inoculated with LacZ gene-modified CT26 cells or parental CT26 cells. The mice immunized with hMIP-1beta gene-modified CT26 tumor vaccine could induce tumor specific CTL activity and nonspecific NK activity, and exhibited resistance to later challenge with wild-type CT26 cells.
CONCLUSIONhMIP-1beta gene-modified CT26 cells exhibit decreased tumorigenicity, and hMIP-1beta gene-modified tumor vaccine may induce a powerful specific and nonspecific antitumor response. The data suggested that hMIP-1beta gene-modified tumor vaccine may play a potent role in prevention of metastasis and recurrence of malignant tumors.
