Format

Send to

Choose Destination
Int J Mol Sci. 2018 Jan 30;19(2). pii: E403. doi: 10.3390/ijms19020403.

Nanobody Based Dual Specific CARs.

Author information

1
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. stijn.demunter@ugent.be.
2
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. joline.ingels@ugent.be.
3
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. glenn.goetgeluk@ugent.be.
4
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. sarahm.bonte@ugent.be.
5
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. melissa.pille@ugent.be.
6
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. karin.weening@ugent.be.
7
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. tessa.kerre@ugent.be.
8
Center for Molecular Medicine Cologne (CMMC) and Departement of Internal Medicine, University of Cologne, 50923 Cologne, Germany. hinrich.abken@uk-koeln.de.
9
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, 9000 Ghent, Belgium. bart.vandekerckhove@ugent.be.

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.

KEYWORDS:

CAR T cell; antigen escape; nanobody

PMID:
29385713
PMCID:
PMC5855625
DOI:
10.3390/ijms19020403
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center