AIMS: Insulin-like growth factor type I (IGF-I) antisense cellular gene therapy of tumours is based on the following data: rat glioma or hepatoma cells transfected with the vector encoding IGF-I antisense cDNA lose their tumorigenicity and induce a tumour specific immune response involving CD8(+) T cells. Recently, using the IGF-I triple helix approach in studies of tumorigenicity, major histocompatibility complex class I (MHC-I) antigens were demonstrated in rat glioma transfected cells. This study used comparative IGF-I antisense and triple helix technologies in human primary glioma cells to determine the triple helix strategy that would be most appropriate for the treatment of glioblastoma. METHODS: The cells were transfected using the IGF-I triple helix expression vector, pMT-AG, derived from the pMT-EP vector. pMT-AG contains a cassette comprising a 23 bp DNA fragment transcribing a third RNA strand, which forms a triple helix structure within a target region of the human IGF-I gene. Using pMT-EP, vectors encoding MHC-I or B7 antisense cDNA were also constructed. RESULTS: IGF-I triple helix transfected glioma cells are characterised by immune and apoptotic phenomena that appear to be related. The expression of MHC-I and B7 in transfected cells (analysed by flow cytometry) was accompanied by programmed cell death (detected by dUTP fluorescein terminal transferase labelling of nicked DNA and electron microscopic techniques). Cotransfection of these cells with MHC-I and B7 antisense vectors suppressed the expression of MHC-I and B7, and was associated with a pronounced decrease in apoptosis. CONCLUSION: When designing an IGF-I triple helix strategy for the treatment of human glioblastoma, the transfected tumour cells should have the following characteristics: the absence of IGF-I, the presence of both MHC-I and B7 molecules, and signs of apoptosis.
AIMS: Insulin-like growth factor type I (IGF-I) antisense cellular gene therapy of tumours is based on the following data: ratglioma or hepatoma cells transfected with the vector encoding IGF-I antisense cDNA lose their tumorigenicity and induce a tumour specific immune response involving CD8(+) T cells. Recently, using the IGF-I triple helix approach in studies of tumorigenicity, major histocompatibility complex class I (MHC-I) antigens were demonstrated in ratglioma transfected cells. This study used comparative IGF-I antisense and triple helix technologies in human primary glioma cells to determine the triple helix strategy that would be most appropriate for the treatment of glioblastoma. METHODS: The cells were transfected using the IGF-I triple helix expression vector, pMT-AG, derived from the pMT-EP vector. pMT-AG contains a cassette comprising a 23 bp DNA fragment transcribing a third RNA strand, which forms a triple helix structure within a target region of the humanIGF-I gene. Using pMT-EP, vectors encoding MHC-I or B7 antisense cDNA were also constructed. RESULTS:IGF-I triple helix transfected glioma cells are characterised by immune and apoptotic phenomena that appear to be related. The expression of MHC-I and B7 in transfected cells (analysed by flow cytometry) was accompanied by programmed cell death (detected by dUTP fluorescein terminal transferase labelling of nicked DNA and electron microscopic techniques). Cotransfection of these cells with MHC-I and B7 antisense vectors suppressed the expression of MHC-I and B7, and was associated with a pronounced decrease in apoptosis. CONCLUSION: When designing an IGF-I triple helix strategy for the treatment of humanglioblastoma, the transfected tumour cells should have the following characteristics: the absence of IGF-I, the presence of both MHC-I and B7 molecules, and signs of apoptosis.
Authors: A Shevelev; P Burfeind; E Schulze; F Rininsland; T R Johnson; J Trojan; C L Chernicky; C Hélène; J Ilan; J Ilan Journal: Cancer Gene Ther Date: 1997 Mar-Apr Impact factor: 5.987
Authors: Mia Carapancea; Oana Alexandru; Ani S Fetea; Laura Dragutescu; Juan Castro; Ada Georgescu; A Popa-Wagner; Magnus L Bäcklund; Rolf Lewensohn; Anica Dricu Journal: J Neurooncol Date: 2008-11-30 Impact factor: 4.130
Authors: Tiphanie Durfort; Mercedes Tkach; Mariya I Meschaninova; Martín A Rivas; Patricia V Elizalde; Alya G Venyaminova; Roxana Schillaci; Jean-Christophe François Journal: PLoS One Date: 2012-01-03 Impact factor: 3.240
Authors: Jerzy Trojan; Yuexin X Pan; Ming X Wei; Adama Ly; Alexander Shevelev; Maciej Bierwagen; Marie-Yvonne Ardourel; Ladislas A Trojan; Alvaro Alvarez; Christian Andres; Maria C Noguera; Ignacio Briceno; Beatriz H Aristizabal; Heliodor Kasprzak; Huynh T Duc; Donald D Anthony Journal: Chemother Res Pract Date: 2012-02-14