Universität zu Köln

Faitschuk, E., Nagy, V., Hombach, A. A. and Abken, H. (2016). 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. Gene Ther., 23 (10). S. 718 - 727. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5462

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Faitschuk, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagy, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-260084
DOI:	10.1038/gt.2016.48
Journal or Publication Title:	Gene Ther.
Volume:	23
Number:	10
Page Range:	S. 718 - 727
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5462
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BIOPHYSICAL PROPERTIES; T-CELLS; TUMOR-CELLS; ACTIVATION; IMMUNORECEPTORS; EXPRESSION; CYTOLYSIS Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26008