title: A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.
abstract: Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the targeting domain in a CAR, while antibodies in the natural format are often available. To overcome the limitation, we designed a CAR that uses an antibody in its natural configuration for binding. Such CAR consists of two chains, the immunoglobulin light and heavy chain with their constant regions, whereby the heavy chain is anchored to the membrane and linked to an intracellular signalling domain for T-cell activation. The two chains form a stable heterodimer, a so-called dual chain CAR (dcCAR), and bind with high affinity and in a specific manner to their cognate antigen. By specific binding, the dcCAR activates engineered T cells for the release of pro-inflammatory cytokines and for target cell lysis. We provide evidence by three examples that the dcCAR format is universally applicable and thereby broadens the CAR cell therapy towards a larger variety of targets for which an scFv antibody is not available.
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Faitschuk
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Nagy
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: A A
authors.initials: AA
authors.lastname: Hombach
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Abken
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; D057127:Single-Chain Antibodies