Grafting T cells with tumor specificity: the chimeric receptor strategy for use in immunotherapy of malignant diseases.

Abstract

Appreciation of the complementary nature of T-cell- and antibody-based immunotherapy stimulated interest in developing approaches that combine their advantages and minimize their limitations. A recent strategy is based on permanent grafting of cytotoxic T cells with a recombinant chimeric receptor designed for cellular targeting with antibody-like specificity and for cellular activation after binding to antigen. The extracellular moiety of the chimeric receptor consists of an antigen-binding domain derived from an antibody, the intracellular moiety consists of a signalling domain for cellular activation, thus combining the broad specificity of antibody-based and major histocompatibility complex (MHC)-independent recognition with the potent antitumor activity of T cells. By generation of specific T cells against any antigen for which a suitable monoclonal antibody (MAb) exists, the chimeric receptor strategy has the potential to extend the adoptive immunotherapy for a variety of malignant and infectious diseases. However, little is known about the optimized design of this type of receptor. We here discuss our results in grafting T cells with chimeric receptors of various design with regard to efficient cellular activation.