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- Title
Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors.
- Authors
McCormack, Emmet; Adams, Katherine; Hassan, Namir; Kotian, Akhil; Lissin, Nikolai; Sami, Malkit; Mujić, Maja; Osdal, Tereza; Gjertsen, Bjørn; Baker, Deborah; Powlesland, Alex; Aleksic, Milos; Vuidepot, Annelise; Morteau, Olivier; Sutton, Deborah; June, Carl; Kalos, Michael; Ashfield, Rebecca; Jakobsen, Bent
- 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-1 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-, NY-ESO-1-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-PCR was 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.
- Subjects
CANCER immunotherapy; IMMUNE response; CYTOTOXIC T cells; T cell receptors; PEPTIDES; CELL surface antigens
- Publication
Cancer Immunology, Immunotherapy, 2013, Vol 62, Issue 4, p773
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-012-1384-4