Universität zu Köln

Hombach, Andreas A., Rappl, Gunter and Abken, Hinrich (2013). Arming Cytokine-induced Killer Cells With Chimeric Antigen Receptors: CD28 Outperforms Combined CD28 OX40 Super-stimulation. Mol. Ther., 21 (12). S. 2268 - 2278. CAMBRIDGE: CELL PRESS. ISSN 1525-0024

Full text not available from this repository.

Abstract

Cytokine-induced killer (CIK) cells raised interest for use in cellular antitumor therapy due to their capability to recognize and destroy autologous tumor cells in a HLA-independent fashion. The antitumor attack of CIK cells, predominantly consisting of terminally differentiated CD8(+)CD56(+) cells, can be improved by redirecting by a chimeric antigen receptor (CAR) that recognizes the tumor cell and triggers CIK cell activation. The requirements for CIK cell activation were, however, so far less explored and are likely to be different from those of younger T cells. We revealed that CD28 and OX40 CARs produced higher interferon- secretion as compared with the first-generation zeta-CAR; CD28-zeta and the third-generation CD28-zeta-OX40 CAR, however, performed similar in modulating most CIK cell effector functions. Compared with the CD28-zeta CAR, however, the CD28-zeta-OX40 CAR accelerated terminal maturation of CD56(+) CIK cells producing high frequencies in activation-induced cell death (AICD) and reduced antitumor efficiency in vivo. Consequently, CD28-zeta CAR CIK cells of CD56(-) phenotype were superior in redirected tumor cell elimination. CAR-mediated CIK cell activation also increased antigen-independent target cell lysis; the CD28-zeta CAR was more efficient than the CD28-zeta-OX40 CAR. Translated into therapeutic strategies, CAR-redirected CIK cells benefit from CD28 costimulation; super-costimulation by the CD28-zeta-OX40 CAR, however, performed less in antitumor efficacy due to increased AICD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rappl, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-470991
DOI:	10.1038/mt.2013.192
Journal or Publication Title:	Mol. Ther.
Volume:	21
Number:	12
Page Range:	S. 2268 - 2278
Date:	2013
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1525-0024
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN T-LYMPHOCYTES; ANTITUMOR-ACTIVITY; ADOPTIVE IMMUNOTHERAPY; TUMOR-GROWTH; HLA BARRIERS; CIK CELLS; COSTIMULATION; CYTOTOXICITY; ACTIVATION; SECRETION Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47099