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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-, NY-ESO-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-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.

Original publication

DOI

10.1007/s00262-012-1384-4

Type

Journal article

Journal

Cancer Immunol Immunother

Publication Date

04/2013

Volume

62

Pages

773 - 785

Keywords

Animals, Antibodies, Bispecific, Antigens, Neoplasm, Antigens, Surface, CD3 Complex, Cell Line, Tumor, Epitopes, Female, HLA-A2 Antigen, Humans, Immunoglobulin Fragments, Lung Neoplasms, Melanoma, Membrane Proteins, Mice, Mice, Inbred NOD, Mice, SCID, Ovarian Neoplasms, Random Allocation, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, T-Lymphocytes, Xenograft Model Antitumor Assays