Universität zu Köln

Chmielewski, Markus and Abken, Hinrich (2015). TRUCKs: the fourth generation of CARs. Expert Opin. Biol. Ther., 15 (8). S. 1145 - 1155. ABINGDON: TAYLOR & FRANCIS LTD. ISSN 1744-7682

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Abstract

Introduction: Adoptive cell therapy of malignant diseases takes advantage of the cellular immune system to recognize and destroy cancer cells. This is impressively demonstrated by redirecting T cells with a chimeric antigen receptor (CAR) towards CD19, inducing complete and lasting remission of leukemia in more than two-thirds of patients in early phase trials. Areas covered: We outline how the CAR strategy is highly specific in redirecting T cells towards pre-defined target cells, however, reaches its limits when targeting solid tumors with a tremendous phenotypic heterogeneity. After initial tumor reduction by CART cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor relapse. The situation may be overcome by CAR-mediated activation of T cells in the tumor, releasing inducible IL-12 which augments T-cell activation and attracts and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion. Expert opinion: CART cells with a transgenic 'payload', so-called TRUCK T cells or the 'fourth-generation' CART cells, are worthwhile to explore to shape the tumor environment by the inducible release of transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be applied in fields beyond cancer therapy including the therapy of virus infections, auto-immune diseases or metabolic disorders.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-398064
DOI:	10.1517/14712598.2015.1046430
Journal or Publication Title:	Expert Opin. Biol. Ther.
Volume:	15
Number:	8
Page Range:	S. 1145 - 1155
Date:	2015
Publisher:	TAYLOR & FRANCIS LTD
Place of Publication:	ABINGDON
ISSN:	1744-7682
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTORS; T-CELL THERAPY; SUICIDE GENE; TUMOR-CELLS; IL-12; INTERLEUKIN-12; ANTITUMOR; ACTIVATION; EXPRESSION; INDUCTION Multiple languages Biotechnology & Applied Microbiology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39806