Universität zu Köln

Chmielewski, Markus, Hombach, Andreas A. and Abken, Hinrich (2014). Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunol. Rev., 257 (1). S. 83 - 91. HOBOKEN: WILEY. ISSN 1600-065X

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Abstract

Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-452261
DOI:	10.1111/imr.12125
Journal or Publication Title:	Immunol. Rev.
Volume:	257
Number:	1
Page Range:	S. 83 - 91
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-065X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DENDRITIC CELLS; HUMAN INTERLEUKIN-12; METASTATIC MELANOMA; SUICIDE GENE; IMMUNE CELLS; IL-12 FAMILY; ACTIVATION; PROLIFERATION; EFFICACY; THERAPY Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45226