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

Abstract

UNLABELLED:

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.

CONCLUSION:

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.

• Authors: Xiao-Ling Luo, Yu-An Xie, Zhi-Peng Kuang, Ji-Ning Wu, An-Min Liang
• Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] (Zhonghua Zhong Liu Za Zhi) Vol. 30 Issue 2 Pg. 97-102 (Feb 2008) ISSN: 0253-3766 [Print] China
• PMID: 18646689 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Chemokine CCL4
• Recombinant Proteins

Topics

• 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