Non-invasive immune imaging and cancer immunotherapy using human PD-L1

Activity: Talk or presentation › Talk or presentation at a conference

Description

Immune checkpoint blocking monoclonal antibodies targeting programmed cell death-1 (PD-1) or its ligand programmed death ligand-1 (PD-L1) have transformed the oncology treatment landscape. PD-1/PD-L1 targeting has improved the prognosis of subsets of patients in a number of cancer types, yet a significant number of patients across different cancer types do not benefit from this immunotherapy. Moreover, the necessity to administer high antibody doses is associated with a high cost and withholds an increased risk of adverse events. To optimize benefit and minimize risks from PD-1/PD-L1 blockade, it is critical to develop innovative agents, theranostics that can be used for patient selection and monitoring as well as for efficient PD-1/PD-L1 blockade at the tumor microenvironment. Nanobodies are small antigen-binding proteins that efficiently penetrate tumors and cell-cell interfaces to bind their antigen with high affinity. Unbound nanobodies are rapidly cleared from blood through renal excretion. Therefore, nanobodies represent promising agents for cancer imaging and therapy. We generated K2, a human PD-L1 specific nanobody, and provided evidence of its theranostic potential. Traits of K2 are (1) high affinity and PD-L1 blocking capacity; (2) competitor for avelumab (Merck KGaA and Pfizer); (3) high signal-to-noise ratio in SPECT/CT imaging of PD-L1+ tumors using 99mTc- or 67Ga-labeled K2; (4) low kidney retention, which is unique as typically nanobodies show high retention in the proximal tubuli; (5) ability to enhance de novo activation of antigen-specific T cells in the setting of cancer vaccination where antibodies fail; and (6) ability to enhance T-cell functionality when interacting with tumor cells. These data advocate the application of K2 in tumor immunotherapy and diagnosis.
Period9 Sep 2021
Event titleNanobodies: Hybrid 2nd edition
Event typeConference
LocationBrussels, Belgium
Degree of RecognitionInternational

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