title: T-cell-receptor-like antibodies - generation, function and applications.
abstract: Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present peptides derived from tumour-associated antigens or viral proteins on their MHC class I molecules. Therefore, disease-specific MHC-peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC-peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity towards tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and serve as valuable research tools for studying MHC class I antigen presentation.
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Rony
authors.initials: R
authors.lastname: Dahan
authors.forename: Yoram
authors.initials: Y
authors.lastname: Reiter
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009363:Neoplasm Proteins / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins / Q000276:immunology; D014777:Virus Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins