Translational & Clinical Research : Visualizing immunosuppressive PD-L1 expression in tumors using anti­ PD-L1 sdAb PET-CT scan: a new strategy for accurate patient selection in targeted immune-activating cancer therapy

PD-L1 is an inhibitory molecule, expressed on a multitude of human solid cancer types. PD-L1 interacts with PD-
1 on the host immune cells. Recently, clinical trials using antibodies that block PD-1–PD-L1 interactions
demonstrated that this treatment was relatively well tolerated, activated immune cells, and can achieve objective
and durable responses in a subset of patients with advanced disease. On the other hand, only 6-27% of patients
effectively benefited from the therapy, and this widely varies per tumor type. Immunohistochemical analyses of
tumor biopsies suggested that non-responsiveness might be due, at least partially, to the lack of in situ tumor
PD-L1 expression. Therefore, the correct selection of patients will be crucial in the future to improve treatment
outcome and reduce morbidity and costs. With this project we aim to develop a PET tracer, 68GaNOTA-Anti-PDL1-
sdAb, to access PD-L1 expression non-invasively as a method to select patients suitable for anti-PD-(L)1
treatment.