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Retrovirus-mediated gene transfer of the cytokine genes interleukin-1beta and tumor necrosis factor-alpha into human neuroblastoma cells: consequences for cell line behavior and immunomodulatory properties.
- Source :
-
European cytokine network [Eur Cytokine Netw] 2001 Mar; Vol. 12 (1), pp. 78-86. - Publication Year :
- 2001
-
Abstract
- We have investigated the value of a gene therapy approach for neuroblastoma (NB), based on retroviral transduction of the IL-1beta or TNF-alpha cytokine genes into human NB lines. Secretion of the corresponding cytokine, was demonstrated in all lines, although with considerable quantitative variations. Cytokine gene expression significantly reduced the proliferation index (p = 0.0001); this effect was associated with either terminal neuronal (one TNF-alpha line) or fibroblast-like differentiation (two IL-1beta lines), leading to growth arrest after a few weeks. Cell surface levels of CD54 and HLA class II remained unaffected, but HLA class I (p < 0.001) and CD58 expression (p = 0.01) increased on SKNSH after TNF-alpha gene transfer. Mononuclear cells from normal allogeneic donors cocultured with both IL-1beta (p < 0.001) and TNF-alpha lines (p < 0.01), showed a significant increase in the proportion of activated T cells (CD3+DR+); however, their cytotoxicity and proliferation rate remained unchanged. Immunotherapy of neuroblastoma will require identification of transduced lines in which cytokine secretion induces phenotypic changes in such a way as to augment their likely immunomodulatory properties without impeding cell growth. Because of the limited efficacy of IL-1beta or TNF-alpha gene transfer alone, further studies should focus on combination with other immunomodulatory agents, to improve their potential efficacy in neuroblastoma.
- Subjects :
- Cell Division
Coculture Techniques
Genetic Vectors
Humans
Lymphocyte Culture Test, Mixed
Lymphocyte Subsets
Neuroblastoma pathology
Phenotype
Tumor Cells, Cultured
Gene Transfer Techniques
Interleukin-1 genetics
Neuroblastoma genetics
Retroviridae genetics
Tumor Necrosis Factor-alpha genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1148-5493
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European cytokine network
- Publication Type :
- Academic Journal
- Accession number :
- 11282550