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

Area of Science:

• Immunology and Oncology
• Biotechnology and Pharmaceutical Sciences

Background:

• The programmed cell death protein 1 (PD-1): programmed death-ligand 1 (PD-L1) pathway is crucial for cancer cells evading immune surveillance.
• Monoclonal antibodies targeting PD-L1 are established cancer therapies, but novel agents are needed for improved diagnosis and treatment.

Purpose of the Study:

• To develop and characterize novel human single domain antibodies (sdAbs) that bind to PD-L1 for potential diagnostic and therapeutic applications.
• To evaluate the affinity, specificity, and in vivo imaging capabilities of a lead sdAb candidate, K2.

Main Methods:

• Generation and selection of human sdAbs against PD-L1.
• Characterization of sdAb K2 affinity and epitope binding using surface plasmon resonance.
• In vivo SPECT/CT imaging in mice using ^99mTc-labeled sdAb K2.
• Assessment of PD-1:PD-L1 blocking activity in human cell-based assays.

Main Results:

• sdAb K2 demonstrated high affinity for human PD-L1 and bound to the same epitope as the therapeutic antibody avelumab.
• ^99mTc-labeled sdAb K2 enabled specific SPECT/CT imaging of PD-L1-expressing tumors in mice with favorable biodistribution and low kidney retention.
• sdAb K2 effectively antagonized PD-1:PD-L1 interactions, enhancing T-cell signaling and tumor cell killing in vitro.

Conclusions:

• sdAb K2 is a promising novel agent with dual diagnostic and therapeutic potential for PD-L1-positive cancers.
• Its specific binding, imaging capabilities, and immune-modulating activity warrant further investigation for clinical translation.