Cancer cells use programmed death-ligand 1 (PD-L1) to paralyze programmed death-1 (PD-1) positive immune cells with anti-cancer functions. Antibodies that bind PD-L1 or its receptor PD-1 evoke durable responses in advanced stage cancer patients. Ever since PD-1:PD-L1 blockade has been intensively studied. We developed a single domain antibody (sdAb) that targets human PD-L1, referred to as K2. Unlike antibodies, sdAbs are small and can therefore penetrate deeper into tumors. Therefore, K2 is an excellent candidate theranostic. We studied K2 for noninvasive imaging of PD-L1 in xenograft cancer models. SPECT/CT imaging showed that K2 labeled with 99m-Technetium has several properties that make K2 an interesting diagnostic, incl. 1) low kidney retention, which is unique for this particular sdAb, as typically sdAbs show high kidney retention at the tubuli, 2) high signal to noise ratio’s, 3) accumulation in PD-L1 positive tumors, and 4) binding to the same epitope on PD-L1 as the FDA-approved antibody Avelumab. Furthermore, we studied the therapeutic value of K2 in vitro, showing that sdAb K2 is able to restore T-cell receptor triggering of T cells when co-cultured with PD-L1 positive tumor cells. Moreover, we used sdAb in the context of dendritic cell (DC) vaccination, showing that sdAb K2 leads to enhanced activation of primary, tumor-specific T-cells when using weakly activated DCs. These preliminary data suggest that K2 is a novel immune checkpoint drug with a strong potential for direct translation from bench to bedside, and warrant further research into K2 and its value as a theranostic.
Originele taal-2English
StatusPublished - 19 okt 2018
EvenementORC day 2018 - Vrije Universiteit Brussel, Jette, Belgium
Duur: 19 okt 201819 okt 2018


ConferenceORC day 2018


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