Universität zu Köln

Faitschuk, Elena, Hombach, Andreas A., Frenzel, Lukas P., Wendtner, Clemens-Martin and Abken, Hinrich (2016). Chimeric antigen receptor T cells targeting Fc mu receptor selectively eliminate CLL cells while sparing healthy B cells. Blood, 128 (13). S. 1711 - 1723. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

Full text not available from this repository.

Abstract

Adoptive cell therapy of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR)-modified T cells targeting CD19 induced lasting remission of this refractory disease in a number of patients. However, the treatment is associated with prolonged on-target off-tumor toxicities due to the targeted elimination of healthy B cells demanding more selectivity in targeting CLL cells. We identified the immunoglobulin M Fc receptor (Fc mu R), also known as the Fas apoptotic inhibitory molecule-3 or TOSO, as a target for a more selective treatment of CLL by CAR T cells. Fc mu R is highly and consistently expressed by CLL cells; only minor levels are detected on healthy B cells or other hematopoietic cells. T cells with a CAR specific for Fc mu R efficiently responded toward CLL cells, released a panel of proinflammatory cytokines and lytic factors, like soluble FasL and granzyme B, and eliminated the leukemic cells. In contrast to CD19 CAR T cells, anti-Fc mu R CAR T cells did not attack healthy B cells. T cells with anti-Fc mu R CAR delayed outgrowth of Mec-1-induced leukemia in a xenograft mouse model. T cells from CLL patients in various stages of the disease, modified by the anti-Fc mu R CAR, purged their autologous CLL cells in vitro without reducing the number of healthy B cells, which is the case with anti-CD19 CAR T cells. Compared with the currently used therapies, the data strongly imply a superior therapeutic index of anti-Fc mu R CAR T cells for the treatment of CLL.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Faitschuk, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frenzel, Lukas P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendtner, Clemens-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-261955
DOI:	10.1182/blood-2016-01-692046
Journal or Publication Title:	Blood
Volume:	128
Number:	13
Page Range:	S. 1711 - 1723
Date:	2016
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; PREVIOUSLY UNTREATED PATIENTS; CD28 COSTIMULATION; PHASE-3 TRIAL; OPEN-LABEL; ACTIVATION; RITUXIMAB; THERAPY; TOSO; IGM Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26195