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Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2002 Jul; Vol. 129 (1), pp. 99-106. - Publication Year :
- 2002
-
Abstract
- We report the immunological characterization of three colon carcinoma cell lines, COLO 205, SW620 and SW403, which we selected to combine with cytokine-secreting fibroblasts for the development of an allogeneic tumour cell vaccine. The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens. They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins. The lines presented TAAs in a manner recognized by immune effector cells, which was demonstrated by the lysis of SW620 by HLA-A2-restricted anti-p53 cytotoxic T lymphocytes (CTL). COLO 205 and SW620 were genetically modified to express the co-stimulatory molecule CD80 (B7.1), which increased the ability of the cells to stimulate CTL in vitro. CTL clones derived from HLA-A2+ peripheral blood mononuclear cells stimulated with the CD80-expressing lines lysed the stimulator cell and an HLA-A2+ colon cancer cell line, but did not lyse an isogeneic fibroblast line or an HLA-A2- colon cancer cell line. CTL clones derived from colon carcinoma patients immunized with an allogeneic vaccine containing these lines demonstrated killing of autologous tumour cells, the vaccine cell lines and other HLA-A2+ colon cancer cell lines, but not fibroblasts isogeneic to certain of the target cell lines. Our studies demonstrate that these colon carcinoma cell lines express shared TAAs that can induce CTLs which recognize and lyse other colon carcinoma cells, and support the continued clinical evaluation of the CD80 gene modified allogeneic colon cell/cytokine-secreting fibroblast carcinoma vaccine.
- Subjects :
- Antigen Presentation
B7-1 Antigen genetics
B7-1 Antigen immunology
Carcinoembryonic Antigen immunology
Cell Adhesion Molecules immunology
Cells, Cultured
Colonic Neoplasms prevention & control
Cytokines metabolism
Cytotoxicity, Immunologic
Epithelial Cell Adhesion Molecule
Fibroblasts immunology
Fibroblasts metabolism
Humans
Lymphocyte Activation
Mucin-1 immunology
Neoplasm Proteins immunology
Receptor, ErbB-2 immunology
Recombinant Fusion Proteins immunology
T-Lymphocytes, Cytotoxic immunology
Transforming Growth Factor beta metabolism
Antigens, Neoplasm immunology
Cancer Vaccines immunology
Colonic Neoplasms immunology
HLA-A2 Antigen immunology
Isoantigens immunology
Tumor Cells, Cultured immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9104
- Volume :
- 129
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 12100028
- Full Text :
- https://doi.org/10.1046/j.1365-2249.2002.01863.x