Universität zu Köln

De Munter, Stijn ORCID: 0000-0003-3821-0620, Ingels, Joline, Goetgeluk, Glenn, Bonte, Sarah, Pille, Melissa ORCID: 0000-0002-2757-6486, Weening, Karin, Kerre, Tessa, Abken, Hinrich and Vandekerckhove, Bart ORCID: 0000-0003-3828-4195 (2018). Nanobody Based Dual Specific CARs. Int. J. Mol. Sci., 19 (2). BASEL: MDPI. ISSN 1422-0067

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Abstract

Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code De Munter, Stijn UNSPECIFIED orcid.org/0000-0003-3821-0620 UNSPECIFIED Ingels, Joline UNSPECIFIED UNSPECIFIED UNSPECIFIED Goetgeluk, Glenn UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonte, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Pille, Melissa UNSPECIFIED orcid.org/0000-0002-2757-6486 UNSPECIFIED Weening, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerre, Tessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Vandekerckhove, Bart UNSPECIFIED orcid.org/0000-0003-3828-4195 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-197157
DOI:	10.3390/ijms19020403
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	19
Number:	2
Date:	2018
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTORS; SINGLE-DOMAIN ANTIBODIES; MODIFIED T-CELLS; B-CELL; IMMUNE ESCAPE; RESISTANCE; IMMUNOTOXINS; SEGREGATION; MUTATIONS; ANTI-CD19 Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19715