dc.contributor.author | McCormack, Emmet | en_US |
dc.contributor.author | Adams, Katherine J. | en_US |
dc.contributor.author | Hassan, Namir J. | en_US |
dc.contributor.author | Kotian, Akhil | en_US |
dc.contributor.author | Lissin, Nikolai M. | en_US |
dc.contributor.author | Sami, Malkit | en_US |
dc.contributor.author | Mujic, Maja | en_US |
dc.contributor.author | Osdal, Tereza | en_US |
dc.contributor.author | Gjertsen, Bjørn Tore | en_US |
dc.contributor.author | Baker, Deborah | en_US |
dc.contributor.author | Powlesland, Alex S. | en_US |
dc.contributor.author | Aleksic, Milos | en_US |
dc.contributor.author | Vuidepot, Annelise | en_US |
dc.contributor.author | Morteau, Olivier | en_US |
dc.contributor.author | Sutton, Deborah H. | en_US |
dc.contributor.author | June, Carl H. | en_US |
dc.contributor.author | Kalos, Michael | en_US |
dc.contributor.author | Ashfield, Rebecca | en_US |
dc.contributor.author | Jakobsen, Bent K. | en_US |
dc.date.accessioned | 2013-03-07T13:49:57Z | |
dc.date.available | 2013-03-07T13:49:57Z | |
dc.date.issued | 2012-12 | eng |
dc.identifier.issn | 1432-0851 | |
dc.identifier.issn | 0340-7004 | |
dc.identifier.uri | https://hdl.handle.net/1956/6397 | |
dc.description | Electronic supplementary material The online version of this article (doi:10.1007/s00262-012-1384-4) contains supplementary material, which is available to authorized users. | eng |
dc.description.abstract | NY-ESO-1 and LAGE-1 are cancer testis antigens with an ideal profile for tumor immunotherapy, combining up-regulation in many cancer types with highly restricted expression in normal tissues and sharing a common HLA-A*0201 epitope, 157–165. Here, we present data to describe the specificity and anti-tumor activity of a bifunctional ImmTAC, comprising a soluble, high-affinity T-cell receptor (TCR) specific for NY-ESO-1157–165 fused to an anti-CD3 scFv. This reagent, ImmTAC-NYE, is shown to kill HLA-A2, antigen-positive tumor cell lines, and freshly isolated HLA-A2- and LAGE-1-positive NSCLC cells. Employing time-domain optical imaging, we demonstrate in vivo targeting of fluorescently labelled high-affinity NYESO-specific TCRs to HLA-A2-, NYESO- 1157–165-positive tumors in xenografted mice. In vivo ImmTAC-NYE efficacy was tested in a tumor model in which human lymphocytes were stably co-engrafted into NSG mice harboring tumor xenografts; efficacy was observed in both tumor prevention and established tumor models using a GFP fluorescence readout. Quantitative RT-PCRwas used to analyze the expression of both NY-ESO-1 and LAGE-1 antigens in 15 normal tissues, 5 cancer cell lines, 10 NSCLC, and 10 ovarian cancer samples. Overall, LAGE-1 RNA was expressed at a greater frequency and at higher levels than NY-ESO-1 in the tumor samples. These data support the clinical utility of ImmTAC-NYE as an immunotherapeutic agent for a variety of cancers. | en_US |
dc.language.iso | eng | eng |
dc.publisher | Springer Verlag | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0/ | eng |
dc.subject | Bi-specific TCR | eng |
dc.subject | ImmTAC | eng |
dc.subject | Cancer immunotherapy | eng |
dc.subject | NY-ESO-1 | eng |
dc.subject | LAGE-1 | eng |
dc.subject | Time-domain | eng |
dc.title | Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | The Author(s) 2012. This article is published with open access at Springerlink.com | |
dc.identifier.doi | https://doi.org/10.1007/s00262-012-1384-4 | |
dc.identifier.cristin | 1034708 | |
dc.source.journal | Cancer Immunology, Immunotherapy | |