title: The emergence of T-bodies/CAR T cells.
abstract: The nickname "T-body" is used to denote a T cell expressing an antigen-specific or antibody-based chimeric receptor that combines antibody specificity with T-cell effector or regulatory function. Initially, we designed and constructed chimeric antibody-based receptors and expressed them in T cells to study the role of major histocompatibility complex in triggering T-cell activation. To this end, we replaced both variable domains (Vα and Vβ of the native T-cell receptor chains) with antibody-derived VH and VL sequences. After transfection into T cells, the 2 chimeric chains paired, associated with the CD3 complex, and endowed transfectants with non-major histocompatibility complex-restricted antibody type specificity. In subsequent studies, we developed next generation of chimeric antibody-based receptors by fusing an antibody single-chain variable fragment to T-cell activation motifs. This modular configuration simplified gene transfer, avoided mixed pairing with endogenous T-cell receptor chains, and enabled simultaneous insertion of various domains as costimulatory moieties to generate T-bodies with efficient antitumor reactivity.
authors.affiliation: From the *Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; †Immunology Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; ‡MIGAL, Galilee Research Institute, Kiryat Shmona, Israel; and §Tel-Hai College, Upper Galilee, Israel.
authors.forename: Zelig
authors.initials: Z
authors.lastname: Eshhar
authors.forename: Tova
authors.initials: T
authors.lastname: Waks
authors.forename: Gideon
authors.initials: G
authors.lastname: Gross
mesh_terms: D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell