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 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.
Hombach
A
A
Klinik I für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, Germany.
Pohl
C
C
Reinhold
U
U
Abken
H
H
D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D000912:Antibodies, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins