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 (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.
Miyazono
Y
Y
Division of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Japan.
Kamogawa
Y
Y
Ryo
K
K
Furukawa
T
T
Mitsuhashi
M
M
Yamauchi
K
K
Kameoka
T
T
Hayashi
N
N
D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D018122:B7-1 Antigen; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D018799:Intercellular Adhesion Molecule-1