C0021158 / AstraZeneca, Cancer Research UK - LARVOL DELTA

[VIRTUAL] Development of a first-in-class Arginase 2 inhibitory monoclonal antibody that restores T cell proliferation in vitro (NCRI 2020) - "Conclusion Specifically, targeting ARG2 in the tumor microenvironment through the application of the novel ARG2 inhibitory antibody C0021158, potentially in combination with standard chemotherapy regimens or alternate immunotherapies, represents a potential new strategy to target immune cold tumors. Impact statement This is the first report of an antibody which can bind to and inhibit the activity of arginase 2 which has been implicated in multiple diseases, in particular those diseases where arginase expression contributes to creating an immune-privileged niche."

IO Biomarker • Preclinical • CNS Disorders • Oncology

Structural and functional characterization of C0021158, a high-affinity monoclonal antibody that inhibits Arginase 2 function via a novel non-competitive mechanism of action. (PubMed, MAbs) - "In silico molecular docking simulations predict that L-arginine is unable to bind effectively when antibody is bound, a prediction supported by isothermal calorimetry experiments using an L-arginine mimetic. Specifically, targeting ARG2 in the tumor microenvironment through the application of C0021158, potentially in combination with standard chemotherapy regimens or alternate immunotherapies, represents a potential new strategy to target immune cold tumors."

IO Biomarker • Journal • Oncology

CR UK, AZ researchers pioneer new antibody maturation technique (PharmaTimes) - "Researchers at the Cancer Research UK-AstraZeneca Antibody Alliance Laboratory in Cambridge, UK, have developed a new technique able to generate an inhibitory, high-affinity antibody against Arginase 2 (ARG2), an enzyme implicated in major human diseases....The lead antibody, called C0021158, is the first product of the researchers’ innovative antibody affinity maturation approach and, according to the researchers, offers a full complement of desirable properties, such as high affinity binding and complete inhibition of ARG2 activity."

Preclinical • Oncology