[Effects of hMIP-1beta gene modification on in vivo tumorigenicity and vaccine efficacy of tumor cells].
OBJECTIVE 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.


METHODS
Murine 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.


RESULTS
hMIP-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.


CONCLUSIONS
hMIP-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.
Luo
Xiao-Ling
XL
Department of Experimental Studies, Affiliated Tumor hospital of Guangxi Medicial University, Nanning 530021, China. lxllc001@sina.com.cn
Xie
Yu-An
YA
Kuang
Zhi-Peng
ZP
Wu
Ji-Ning
JN
Liang
An-Min
AM
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D054407:Chemokine CCL4 / Q000235:genetics* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D047368:Tumor Burden
D019496:Cancer Vaccines; D054407:Chemokine CCL4; D011994:Recombinant Proteins