Augmented Systemic Immunity in Mice Implanted with Tumor Necrosis Factor-alpha Gene-transduced Meth-A-cells

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1994 Mar 1

PMID 8188531

Citations 3

Authors

S Fujii

Y Liu

H Neda

Y Itoh

Y Koshita

M Takahashi

N Watanabe

Y Kohgo

Y Niitsu

Affiliations

Soon will be listed here.

Abstract

Syngeneic BALB/c mice bearing methylcholanthrene-induced fibrosarcoma (Meth-A) cells transduced with a tumor necrosis factor (TNF) gene showed a longer life span and tumor regression as compared with mice carrying TNF-non-producing Meth-A cells. To elucidate the mechanism of the reduced tumorigenicity of TNF-producing Meth-A, we compared systemic immune responses between mice bearing high TNF producer (C5) and unmodified Meth-A cells (M0). The results indicated that the cytotoxic activity of lymphokine-activated killer cells (LAK) induced from spleen cells of mice bearing C5 was higher against both M0 and C5 than that of LAK from mice bearing M0. Also, C5 was more sensitive to LAK induced from spleen cells of C5- and M0- bearing mice than M0. We also found that cytotoxic T lymphocyte from spleen cells of mice transplanted with C5 was more cytotoxic to M0 than that from mice with M0. In addition, the population of Lyt2 (CD8)-positive T cells was higher in freshly isolated spleen cells of mice transplanted with C5 than from mice with M0. Finally, we observed a higher expression of MHC class 1 antigen on C5 than on M0. These observations suggest that the augmented host systemic immunity in mice carrying TNF gene-modified Meth-A cells is one of the mechanisms of the reduced tumorigenicity of C5 and that the increased systemic immunity can be ascribed to the increased immunogenicity of the tumor cells. Thus, the use of TNF gene-modified tumor cells as vaccines appears to be promising for therapeutic and/or prophylactic application.

Citing Articles

Development of a serum-free medium for a human immortalized fibroblast cell line (KMST-6/TNF) producing tumor necrosis factor-alpha (TNF-alpha) and growth inhibitory effects of its conditioned medium on malignant cells in culture.

Oh S, Miyazaki M, Namba M In Vitro Cell Dev Biol Anim. 2001; 37(3):169-71.

PMID: 11370808 DOI: 10.1290/1071-2690(2001)037<0169:DOASFM>2.0.CO;2.

Establishment of a human fibroblast cell line producing tumor necrosis factor alpha (KMST-6/TNF) and growth inhibitory effects of its conditioned medium on malignant cells in culture.

Fushimi K, Torigoe K, Yamauchi H, Furusako S, Kurimoto M, Namba M In Vitro Cell Dev Biol Anim. 1998; 34(6):463-7.

PMID: 9661049 DOI: 10.1007/s11626-998-0079-9.

Characterization of tumor-necrosis-factor-gene-transduced tumor-infiltrating lymphocytes from ascitic fluid of cancer patients: analysis of cytolytic activity, growth rate, adhesion molecule expression and cytokine production.

Itoh Y, Koshita Y, Takahashi M, Watanabe N, Kohgo Y, Niitsu Y Cancer Immunol Immunother. 1995; 40(2):95-102.

PMID: 7882388 PMC: 11037740. DOI: 10.1007/BF01520290.

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