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

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: Cancers (Basel)
ISSN: 2072-6694
Issue: 6
Volume: 11
Jaar van publicatie:2019
Trefwoorden:Cancer, Immunotherapy, Immune Checkpoint, PD-L1
  • ORCID: /0000-0001-9220-4833/work/88545790
  • ORCID: /0000-0002-9065-1549/work/69373228
  • ORCID: /0000-0001-8824-0452/work/62387725
  • ORCID: /0000-0001-9006-1074/work/62359717
  • ORCID: /0000-0002-2627-0880/work/62231109
  • ORCID: /0000-0002-9999-8557/work/62120232
  • ORCID: /0000-0002-8895-9763/work/61471767
  • ORCID: /0000-0002-9997-4571/work/61029061
  • WoS Id: 000475351200136
  • Scopus Id: 85070642138
  • DOI: https://doi.org/10.3390/cancers11060872
CSS-citation score:2
Toegankelijkheid:Open