![]() ![]() LTR, long terminal repeat Ψ, extended packaging signal sd, splice donor sa, splice acceptor Alpha, alpha chain IRES, internal ribosomal entry site Beta, beta chain. ![]() ( B) Diagram of the recombinant retroviral vector MSGV1AIB used to engineer human lymphocytes. Values demonstrating the specific release of cytokine are in bold. Effector T cells were cocultured with T2 cells pulsed with 1 μM of the indicated peptide (values are expressed as IFN-γ in pg/ml). ( A) CD8 +human lymphocytes were electroporated with RNA encoding control or cloned TCRs reactive with HLA-A2 restricted epitopes from the human TAAs MART-1, gp100, NY-ESO-1, and p53. Transduction and analysis of TCR-engineered cells. Furthermore, transduction with these TCR-encoding retro-viral vectors converted normal PBLs into cells capable of specifically recognizing and destroying both fresh and cultured cells from multiple common cancers (such as sarcoma and breast, lung, esophagus, and liver cancers) in vitro (–). 1A) and were able to recognize HLA-A2–matched tumors, including melanoma, lung cancer, and breast cancer (table S1). These transfected cells produced large amounts of interferon-γ (IFN-γ) upon stimulation with their respective peptides ( Fig. ![]() In vitro transcribed RNA from four TAA-reactive TCRs (recognizing MART-1: 27–35, gp100: 209–217, NY-ESO-1: 157–165, and p53: 264–272) were electroporated into CD8 + PBLs, which were then cocultured with peptide-pulsed T2 cells. In each case, these antigens were detected by the TCR when they were presented as peptides by molecules encoded by the major histocompatibility complex protein human lymphocyte antigen (HLA)–A2. ![]() The genes encoding the TCR that are specific for a variety of TAA have now been cloned, including the TCR-recognizing MART-1 and gp100 melanoma/melanocyte differentiation antigens, the NY-ESO-1 cancer-testis antigen that is present on many common epithelial cancers, and an epitope from the p53 molecule, which is expressed on the surface of approximately 50% of cancers of common epithelial origin (–). Tumor-associated antigens (TAAs) are recognized by the T cell receptor (TCR) on the T lymphocyte surface, which is composed of the TCR alpha and beta chains (). ![]()
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