Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunologic properties with interleukin-2.
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)beta 1. 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.
Miller
A R
AR
Division of Surgical Oncology, Jonsson Comprehensive Center, UCLA Medical Center 90024-1782.
McBride
W H
WH
Dubinett
S M
SM
Dougherty
G J
GJ
Thacker
J D
JD
Shau
H
H
Kohn
D B
DB
Moen
R C
RC
Walker
M J
MJ
Chiu
R
R
D000818:Animals; D000951:Antigens, Neoplasm; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D004279:DNA, Viral / Q000096:biosynthesis; D018014:Gene Transfer Techniques; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D015851:Interleukin-7 / Q000096:biosynthesis / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016662:Virus Integration
D000951:Antigens, Neoplasm; D017931:DNA Primers; D004279:DNA, Viral; D007376:Interleukin-2; D015851:Interleukin-7; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta