Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells

Background : The induction of tumour‐specific immunity is important for advanced cancer therapy. There are many molecules, including costimulatory molecules, that have been identified as the activator for tumour‐specific T cells. Methods : To induce autologous tumour‐specific cytotoxic T lymphocytes...

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Published in:	Journal of gastroenterology and hepatology Vol. 14; no. 10; pp. 997 - 1003
Main Authors:	Miyazono, Yuko, Kamogawa, Yumiko, Ryo, 1 Kyouka, Furukawa, Takaji, Mitsuhashi, Maki, Yamauchi, Katsumi, Kameoka, Takanobu, Hayashi, Naoaki
Format:	Journal Article
Language:	English
Published:	Melbourne, Australia Blackwell Science Pty 01-10-1999 Blackwell Science
Subjects:	B7-1 Antigen - biosynthesis B7-1 Antigen - genetics Biological and medical sciences CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Cell Division - drug effects Cell Division - immunology Cells, Cultured co-stimulatory signal Colonic Neoplasms - genetics Colonic Neoplasms - immunology Colonic Neoplasms - pathology cytotoxic T lymphocyte Cytotoxicity Tests, Immunologic Epitopes Female Flow Cytometry Histocompatibility Antigens Class I - biosynthesis Humans Immunopathology Immunotherapy (general aspects) Intercellular Adhesion Molecule-1 - biosynthesis Interleukin-2 - pharmacology Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Lymphocyte Activation - genetics Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Medical sciences Middle Aged T-Lymphocytes, Cytotoxic - immunology Transfection tumour immunity Human Immune response Induction Cytotoxicity Tumor infiltrating lymphocyte Malignant tumor Colonic disease Cell line Immunotherapy Adoptive immunity Digestive diseases Intestinal disease Colon
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Summary:	Background : The induction of tumour‐specific immunity is important for advanced cancer therapy. There are many molecules, including costimulatory molecules, that have been identified as the activator for tumour‐specific T cells. Methods : To induce autologous tumour‐specific cytotoxic T lymphocytes (CTL) more effectively, we studied whether the expression of the B7 gene may render human colon cancer cells able to stimulate autologous peripheral blood mononuclear cells (PBMC) to become tumour‐specific cytotoxic T cells. After the establishment of a B7.1 gene transfected tumour cell line, Cw2/B7.1, we first examined its stimulatory effect on autologous PBMC and subsequently, its effect on the induction of parental cell (Cw2)‐specific CTL. Results : The results showed that Cw2/B7.1 had a more potent stimulatory effect on PBMC for the induction of both proliferation and cytotoxicity than Cw2. By adding a low dose of interleukin‐2, Cw2/B7.1‐activated killer cell activity was significantly increased. The specificity of Cw2/B7.1‐activated killer cells was demonstrated by the absence of their cytotoxicity to either human lymphocyte antigen (HLA)‐A33 identical (ORF) or HLA‐non‐identical (MT) allogenic colon cancer cell lines. Furthermore, such Cw2‐specific cytotoxic activity was significantly reduced by the deletion of CD8+ cells but not CD4+ cells, indicating that these killer cells were mainly CD8+ T cells. Conclusions : Thus, our results demonstrate that, by using B7.1 gene‐transfected tumour cell lines, we effectively induced autologous tumour‐specific CTL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients. © 1999 Blackwell Science Asia Pty Ltd
Bibliography:	ark:/67375/WNG-BFCNJ39H-Q istex:4AA50B33E135BFDF8408B2BCFBB1DC701ACD9388 ArticleID:JGH1990 Current address: Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4‐6‐1 Shiroganedai Minato‐ku Tokyo 108‐8639, Japan. 1
ISSN:	0815-9319 1440-1746
DOI:	10.1046/j.1440-1746.1999.01990.x