Transduction of human melanoma cell lines with the human interleukin-7 gene
using retroviral-mediated gene transfer: comparison of immunologic
properties with interleukin-2
AR Miller, WH McBride, SM Dubinett, GJ Dougherty, JD Thacker, H Shau, DB Kohn, RC Moen, MJ Walker and R Chiu
Division of Surgical Oncology, Jonsson Comprehensive Center, UCLA Medical
Center 90024-1782.
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.
Volume 82,
Issue 12,
pp. 3686-3694,
12/15/1993
Copyright © 1993 by The American Society of Hematology
