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.