Transfection of IL-2 Augments CTL Response to Human Melanoma Cells In Vitro
| Autor: | Suzanne Osanto, Peter I. Schrier, Carolien E. van der Minne, Corlien A. Aarnoudse, Corry W. van der Spek, Nathalie Brouwenstijn, Andrea van Elsas |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Immunology Melanoma Experimental Clone (cell biology) chemical and pharmacologic phenomena Biology Transfection Cancer Vaccines Peripheral blood mononuclear cell Melanoma Vaccine Antigen Tumor Cells Cultured medicine Humans Immunology and Allergy Cytotoxic T cell Pharmacology Melanoma Histocompatibility Antigens Class II Granulocyte-Macrophage Colony-Stimulating Factor hemic and immune systems Genetic Therapy medicine.disease CTL Head and Neck Neoplasms Cell culture Cancer research Interleukin-2 Immunotherapy T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Immunotherapy. 20:343-353 |
| ISSN: | 1524-9557 |
| Popis: | We have transfected human melanoma cell line 518A2 with the cDNA encoding interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF), and compared cytokine-producing clones for their ability to induce melanoma-specific cytotoxic T lymphocytes (CTL) from autologous peripheral blood mononuclear cells (PBMC) in vitro. The parental cell line expressed HLA-A1, HLA-A2, ICAM-I, LFA-3, in addition to the common CTL antigens MAGE-I, MAGE-3, tyrosinase, gp100, and Melan-A/MART-1. Stimulation of autologous PBMC responders with the IL-2-transfected clone 518/IL2.14 specifically induced CTL lines reactive with all cell lines derived from the autologous patient. Strikingly, GM-CSF-transfected 518A2 cells did not induce anti-tumor CTL reactivity. CTL induction against 518/ IL2.14 was independent of HLA class II expression or CD4 help. The parental cell line 518A2 gained immunogenic properties when high concentrations of IL-2 were supplied exogenously, indicating that IL-2 produced and present at high levels locally by itself enhanced immunogenicity. From the autologous CTL line reactive with 518/ IL2.14, clones were generated against an as yet unknown antigen, which was present in all autologous melanoma cell lines as well as in 7 of 15 HLA-A2 + melanoma cell lines tested, but not in melanocytes. These results will be discussed with respect to the possibility of using IL-2-transfected melanoma cells as a vaccine for treatment of patients with melanoma. |
| Databáze: | OpenAIRE |
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