Universität zu Köln

Rudek, Loreen Sophie, Zimmermann, Katharina, Galla, Melanie, Meyer, Johann, Kuehle, Johannes, Stamopoulou, Andriana, Brand, Daniel, Sandalcioglu, I. Erol, Neyazi, Belal, Moritz, Thomas, Rossig, Claudia, Altvater, Bianca, Falk, Christine S., Abken, Hinrich, Morgan, Michael Alexander and Schambach, Axel (2021). Generation of an NF kappa B-Driven Alpharetroviral All-in-One Vector Construct as a Potent Tool for CAR NK Cell Therapy. Front. Immunol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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Abstract

Immune cell therapeutics are increasingly applied in oncology. Especially chimeric antigen receptor (CAR) T cells are successfully used to treat several B cell malignancies. Efforts to engineer CAR T cells for improved activity against solid tumors include co-delivery of pro-inflammatory cytokines in addition to CARs, via either constitutive cytokine expression or inducible cytokine expression triggered by CAR recognition of its target antigen-so-called T cells redirected for universal cytokine-mediated killing (TRUCKs) or fourth-generation CARs. Here, we tested the hypothesis that TRUCK principles could be expanded to improve anticancer functions of NK cells. A comparison of the functionality of inducible promoters responsive to NFAT or NF kappa B in NK cells showed that, in contrast to T cells, the inclusion of NF kappa B-responsive elements within the inducible promoter construct was essential for CAR-inducible expression of the transgene. We demonstrated that GD2CAR-specific activation induced a tight NF kappa B-promoter-driven cytokine release in NK-92 and primary NK cells together with an enhanced cytotoxic capacity against GD2(+) target cells, also shown by increased secretion of cytolytic cytokines. The data demonstrate biologically relevant differences between T and NK cells that are important when clinically translating the TRUCK concept to NK cells for the treatment of solid malignancies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rudek, Loreen Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmermann, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Galla, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Johann UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehle, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamopoulou, Andriana UNSPECIFIED UNSPECIFIED UNSPECIFIED Brand, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandalcioglu, I. Erol UNSPECIFIED UNSPECIFIED UNSPECIFIED Neyazi, Belal UNSPECIFIED UNSPECIFIED UNSPECIFIED Moritz, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rossig, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Altvater, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Falk, Christine S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgan, Michael Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schambach, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596656
DOI:	10.3389/fimmu.2021.751138
Journal or Publication Title:	Front. Immunol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; T-CELLS; TRANSGENE EXPRESSION; CANCER; ACTIVATION; IMMUNOTHERAPY; HETEROGENEITY; REMISSIONS; LIGAND Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59665