Preclinical Characterization of a Novel Anti-Cancer PD-L1 Inhibitor RPH-120

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Programmed death-ligand 1 (PD-L1) is a key immune checkpoint target in cancer immunotherapy.
• Novel monoclonal antibodies targeting PD-L1 aim to restore anti-tumor immune responses.
• RPH-120 is a novel fully human IgG1 monoclonal antibody engineered against PD-L1.

Purpose of the Study:

• To characterize the binding affinity, cross-reactivity, bioactivity, and antitumor efficacy of RPH-120.
• To evaluate the safety and toxicokinetic profile of RPH-120 in preclinical models.

Main Methods:

• Surface plasmon resonance assays to determine binding affinity to monomeric and dimeric PD-L1.
• Mixed lymphocyte reaction assay to assess T cell activation.
• In vivo efficacy studies in HCC-827 lung cancer xenografts in humanized mice.
• Toxicity and toxicokinetic studies in Cynomolgus monkeys.

Main Results:

• RPH-120 exhibited significantly higher affinity for dimeric human PD-L1 and bound to human and monkey PD-L1, but not mouse PD-L1.
• RPH-120 demonstrated T cell activation in vitro and significant tumor growth inhibition in vivo, comparable to atezolizumab.
• RPH-120 showed an acceptable toxicokinetic profile and was well-tolerated up to 200 mg/kg in Cynomolgus monkeys.

Conclusions:

• RPH-120 is a potent anti-PD-L1 antibody with promising in vitro and in vivo antitumor activity.
• The antibody demonstrated favorable safety and pharmacokinetic profiles in preclinical studies.
• RPH-120 represents a potential novel drug candidate for cancer immunotherapy.