Transduction of Human Melanoma Cell Lines With the Human Interleukin-7 Gene Using Retroviral-Mediated Gene Transfer: Comparison of Immunologic Properties With Interleukin-2

• Published in: Blood 1993-12, Vol.82 (12), p.3686-3694
• Main Authors: Miller, Alexander R., McBride, William H., Dubinett, Steven M., Dougherty, Graeme J., Thacker, J. Dean, Shau, Hungyi, Kohn, Donald B., Moen, Robert C., Walker, Michael J., Chiu, Robert, Schuck, Beatrice L., Rosenblatt, Joseph A., Huang, Min, Dhanani, Shawkat, Rhoades, Kristina, Economou, James S.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm; Antineoplastic agents; Base Sequence; Biological and medical sciences; Cell Division; Cell Line; Cytotoxicity, Immunologic; DNA Primers; DNA, Viral - biosynthesis; Gene Transfer Techniques; Humans; Immunotherapy; Interleukin-2 - biosynthesis; Interleukin-2 - metabolism; Interleukin-7 - biosynthesis; Interleukin-7 - metabolism; Medical sciences; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Melanoma-Specific Antigens; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Proteins - analysis; Neoplasm Proteins - biosynthesis; Neoplasm Transplantation; Pharmacology. Drug treatments; Polymerase Chain Reaction; Retroviridae - genetics; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - biosynthesis; Transplantation, Heterologous; Tumor Cells, Cultured; Virus Integration
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.12.3686.3686

Two human melanoma cell lines were transduced with the human interleukin (IL)-7 and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level cytokine expression was achieved. The in vitro growth of transduced tumors was unaltered. Neither of the IL-2-transduced melanoma cell lines grew in athymic mice, whereas one IL-7–transduced melanoma line showed retarded in vivo growth. This is consistent with animal studies suggesting a predominantly T-cell response to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced tumors. Both IL-7– and IL-2–transduced melanoma cell lines could induce cytotoxic lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In one cell line, IL-7 transduction resulted in a marked inhibition of the immunosuppressive peptide transforming growth factor (TGF)β1. The results allow a comparison of immunobiologic properties of IL-7– and IL-2–transduced human melanoma cell lines in consideration of their use in genetically engineered tumor vaccines. IL-7 transduction results in stable cytokine expression and phenotypic alterations that appear to be favorable for enhanced immunogenicity and it deserves clinical testing.