Universität zu Köln

Bunse, Mario ORCID: 0000-0002-7554-2520, Pfeilschifter, Janina, Bluhm, Julia, Zschummel, Maria, Joedicke, Jara J., Wirges, Anthea, Stark, Helen ORCID: 0000-0002-5726-3958, Kretschmer, Vivien, Chmielewski, Markus, Uckert, Wolfgang, Abken, Hinrich, Westermann, Joerg, Rehm, Armin ORCID: 0000-0001-7490-1950 and Hoepken, Uta E. (2021). CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin's lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME. CAR-T cell therapy targeting CD19 is not as efficient to treat lymphoma with nodal dissemination as it is for B cell leukaemia. Here, the authors generate CAR-T cells against CXCR5 and show they inhibit tumour growth by depleting both B and follicular T helper cells in lymphoma models.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bunse, Mario UNSPECIFIED orcid.org/0000-0002-7554-2520 UNSPECIFIED Pfeilschifter, Janina UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluhm, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zschummel, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Joedicke, Jara J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirges, Anthea UNSPECIFIED UNSPECIFIED UNSPECIFIED Stark, Helen UNSPECIFIED orcid.org/0000-0002-5726-3958 UNSPECIFIED Kretschmer, Vivien UNSPECIFIED UNSPECIFIED UNSPECIFIED Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Uckert, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Westermann, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehm, Armin UNSPECIFIED orcid.org/0000-0001-7490-1950 UNSPECIFIED Hoepken, Uta E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592706
DOI:	10.1038/s41467-020-20488-3
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOKINE RECEPTOR; MATURATION ANTIGEN; THERAPY; MICROENVIRONMENT; EXPRESSION; IMMUNOTHERAPY; ACTIVATION; RITUXIMAB; SURVIVAL Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59270