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

Appreciation of the complementary nature of T-cell- and antibody-based immu notherapy stimulated interest in developing approaches that combine their a dvantages and minimize their limitations, A recent strategy is based on per manent grafting of cytotoxic T cells with a recombinant chimeric receptor d esigned for cellular targeting with antibody-like specificity and for cellu lar activation after binding to antigen, The extracellular moiety of the ch imeric receptor consists of an antigen-binding domain derived from an antib ody, the intracellular moiety consists of a signalling domain for cellular activation, thus combining the broad specificity of antibody-based and majo r histocompatibility complex (MHC)-independent recognition with the potent antitumor activity of T cells, By generation of specific T cells against an y antigen for which a suitable monoclonal antibody (MAb) exists, the chimer ic receptor strategy has the potential to extend the adoptive immunotherapy for a variety of malignant and infectious diseases. However, little is kno wn 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.