Deciphering AK119: Unleashing the Potential of Anti-CD73 Immunotherapy in Combating COVID-19

CD73, an enzyme that plays a role in ATP metabolism by converting AMP to adenosine, is a target for a new monoclonal antibody, AK119, developed to combat COVID-19. The SARS-CoV-2 virus hinders interferon activity, which is crucial for a robust anti-viral response and can lead to severe respiratory issues and lung injury due to excess adenosine. By inhibiting CD73, extracellular ATP levels may rise, which could counteract the effects of COVID-19. Additionally, blocking CD73 has been shown to activate lymphocytes, stimulate B cells to produce antibodies, and improve lymphocyte movement, potentially enhancing the production of anti-SARS-CoV-2 antibodies for virus clearance.

AK119's ability to bind to CD73 and inhibit its enzymatic activity was assessed using various assays, demonstrating high affinity and comparable or superior performance to another leading anti-CD73 antibody, 10.3AA. AK119 showed high inhibition rates and effectively induced CD73 internalization in tested cell lines, with rates exceeding those of 10.3AA. Furthermore, AK119 significantly increased the expression of activation markers CD69 and CD83 on B cells and promoted a substantial increase in IgG production.

The study concludes that AK119 exhibits complete inhibition of CD73 and induces significant B cell activation and antibody production, showing promising preclinical bioactivities. An upcoming Phase 1 clinical trial (NCT04516564) will evaluate the safety and pharmacokinetics of AK119 in healthy volunteers.