Format

Send to

Choose Destination
Cancers (Basel). 2019 Jun 21;11(6). pii: E872. doi: 10.3390/cancers11060872.

Evaluating a Single Domain Antibody Targeting Human PD-L1 as a Nuclear Imaging and Therapeutic Agent.

Author information

1
Laboratory for Molecular and Cellular therapy (LMCT), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. katrijn.broos@vub.ac.be.
2
Laboratory for Molecular and Cellular therapy (LMCT), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. quentin.lecocq@vub.be.
3
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. catarina.xavier@vub.be.
4
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Jessica.Bridoux@vub.be.
5
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. thamnt.vn@gmail.com.
6
Laboratory of Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. thamnt.vn@gmail.com.
7
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research Center, Brussels, Pleinlaan 2, B-1050 Brussels, Belgium. thamnt.vn@gmail.com.
8
Laboratory for Molecular and Cellular therapy (LMCT), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. jurgen.corthals@vub.be.
9
Laboratory of Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. steve.schoonooghe@vub.vib.be.
10
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research Center, Brussels, Pleinlaan 2, B-1050 Brussels, Belgium. steve.schoonooghe@vub.vib.be.
11
Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. eva.lion@uantwerpen.be.
12
Center for Cell Therapy and Regenerative Medicine, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Antwerp, Belgium. eva.lion@uantwerpen.be.
13
Laboratory of Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. geert.raes@vub.be.
14
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research Center, Brussels, Pleinlaan 2, B-1050 Brussels, Belgium. geert.raes@vub.be.
15
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. marleen.keyaerts@uzbrussel.be.
16
Department of Nuclear Medicine (NUGE), UZ Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium. marleen.keyaerts@uzbrussel.be.
17
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. ndevoogd@vub.be.
18
Laboratory for Molecular and Cellular therapy (LMCT), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. karine.breckpot@vub.be.

Abstract

The PD-1:PD-L1 immune checkpoint axis is central in the escape of cancer cells from anticancer immune responses. Monoclonal antibodies (mAbs) specific for PD-L1 have been approved for treatment of various cancer types. Although PD-L1 blockade has proven its merit, there are still several aspects that require further attention to fully capitalize on its potential. One of these is the development of antigen-binding moieties that enable PD-L1 diagnosis and therapy. We generated human PD-L1 binding single domain antibodies (sdAbs) and selected sdAb K2, a sdAb with a high affinity for PD-L1, as a lead compound. SPECT/CT imaging in mice following intravenous injection of Technetium-99m (99mTc)-labeled sdAb K2 revealed high signal-to-noise ratios, strong ability to specifically detect PD-L1 in melanoma and breast tumors, and relatively low kidney retention, which is a unique property for radiolabeled sdAbs. We further showed using surface plasmon resonance that sdAb K2 binds to the same epitope on PD-L1 as the mAb avelumab, and antagonizes PD-1:PD-L1 interactions. Different human cell-based assays corroborated the PD-1:PD-L1 blocking activity, showing enhanced T-cell receptor signaling and tumor cell killing when PD-1POS T cells interacted with PD-L1POS tumor cells. Taken together, we present sdAb K2, which specifically binds to human PD-L1, as a new diagnostic and therapeutic agent in cancer management.

KEYWORDS:

PD-1; PD-L1; T cell; avelumab; cancer; immune checkpoint; immunotherapy; monoclonal antibody; nanobody; single domain antibody

PMID:
31234464
DOI:
10.3390/cancers11060872
Free full text

Supplemental Content

Full text links

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