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- Title
Increase in proliferation rate and normalization of TNF-α secretion by blockage of gene transfer–induced apoptosis in lymphocytes using low-dose cyclosporine A.
- Authors
Röpke, Gabriele; Ebert, Oliver; Märten, Angela; Lefterova, Petja; Micka, Bettina; Buttgereit, Peter; Niemitz, Sigrun; Trojaneck, Beate; Schmidt-Wolf, Gabriele; von Rücker, Alexander; Huhn, Dieter; Wittig, Burghardt; Schmidt-Wolf, Ingo GH
- Abstract
Efficient gene transfer of lymphocytes is extremely difficult. We have shown previously that induction of apoptosis may play a role in the gene transfer resistance of lymphocytes. Anti-CD3 antibody can be used as a surrogate for receptor-mediated gene transfer in T lymphocytes. However, anti-CD3 antibody has been shown to be the causative agent of apoptosis in receptor-mediated gene transfer. In this study, we show that blockage of apoptosis by addition of low-dose cyclosporine A can lead to normalization of elevated TNF-α secretion and to a significant increase in the proliferation rate of transfected lymphocytes. In contrast, this had no negative effect on cytotoxic activity of immunologic effector cells called cytokine-induced killer cells. Therefore, blockage of apoptosis should have an impact on the use of lymphocytes transfected with cytokine genes as immunologic effector cells in cancer gene therapy protocols.
- Subjects
CYCLOSPORINE; TUMOR necrosis factors; GENETIC transformation; APOPTOSIS
- Publication
Cancer Gene Therapy, 2000, Vol 7, Issue 11, p1411
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700256