Transduction of human melanoma cells with the gamma interferon gene enhances cellular immunity
Abdel-Wahab, Z.A.; Osanto, S.; Darrow, T.L.; Barber, J.R.; Vervaert, C.E.; Gangavalli, R.; McCallister, T.J.; Seigler, H.F.
Cancer Gene Therapy 1(3): 171-179
1994
ISSN/ISBN: 0929-1903 PMID: 7621248 Document Number: 435369
Human tumor cells transduced with the gamma interferon (gamma-IFN) gene are currently used in specific active immunotherapy protocols to enhance the antitumor immune responses of cancer patients. This in vitro study was undertaken to examine the initial events in the cellular immune response that may occur following the administration of the gamma-IFN-transduced cell vaccine. Human melanoma tumor cell lines were transduced with a MoMLV-based retroviral vector carrying the human gamma-IFN gene. The transduced cells expressed the cytokine gene, secreted biologically active gamma-IFN, and exhibited enhanced expression of MHC class I and class II (HLA-DR), and ICAM-1 surface antigens. The gamma-IFN-transduced and corresponding parental melanoma cells were used for the induction of short-term lymphocyte cultures. Peripheral blood lymphocytes or lymph node cells from 20 melanoma patients were stimulated for 5 to 15 days with autologous or MHC class 1-matched allogeneic parental or gamma-IFN-transduced melanoma cells. Seven of the 20 lymphocyte cultures showed substantial increases in lyric activity following stimulation with the transduced melanoma cells in comparison to control lymphocyte cultures stimulated with unmodified parental melanoma. The cytolytic activity stimulated with gamma-IFN-modified melanomas was mediated partly by MHC-restricted cytotoxic T lymphocytes and partly by NK cells. Lymphocyte cultures that displayed increases in cytotoxicity after stimulation with the gamma-IFN-transduced melanoma cells also exhibited enhanced expression or induction of one or more of the following lymphokines: IL-4, IL-1-alpha, IL-1-beta, gamma-IFN, and TNF-alpha. Under these conditions of short-term cultures, the clonal expansion of lymphocytes stimulated with the gamma-IFN-modified cells increased an average of 1.7-fold over control cultures stimulated with parental cells. The data provide a rationale for the use of gamma-IFN-modified cells as a vaccine for melanoma patients and as an immunogen for the induction of effector cells for adoptive immunotherapy of malignant melanoma.