Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity in vivo
Year: 2025
Type: article
Abstract: The monoclonal antibody rituximab functions through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) and is used to treat non-Hodgkin’s lymphoma. Elevated serum CA125/MUC16 levels, present in some follicular lymphoma patients, have been shown to correlate with reduced efficacy of rituximab. Previous studies revealed that CA125/MUC16 binds to rituximab, diminishing its CDC and ADCC. A rituximab variant, NAV-006, was engineered to counteract CA125/MUC16’s immunosuppressive effects. NAV-006 demonstrated enhanced CDC and ADCC activities and was unaffected by CA125/MUC16. In the present study, NAV-006 showed improved in vivo antitumor activity compared to rituximab in a human lymphoma model with reconstituted CA125/MUC16. Additionally, CA125/MUC16 bound to newer antibody-based lymphoma treatment agents, including obinutuzumab and tafasitamab, suppressing their immune effector functions. Bispecific antibodies mosunetuzumab and glofitamab also exhibited reduced cytotoxicity in the presence of CA125/MUC16. These findings suggest that NAV-006 could improve therapeutic efficacy in B-cell lymphomas, particularly in patients with elevated CA125/MUC16 levels.
Source: Antibody Therapeutics
DOI: 10.1093/abt/tbaf008
Authors: Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,822
OpenAlex ID: W4409765845