Rituximab (RTX) is a CD20-targeting antibody that is the standard-of-care for patients with non-Hodgkin Lymphoma (NHL) cases. Furthermore, the study characterized an RTX variant, named NAV-006 (RTX-N109D), which was more refractory to the immunosuppressive effects mediated by CA125 as evidenced by its reduced CA125 interaction and increased activity of ADCC and CDC when compared with parent RTX. Taken together, these findings warranted further investigation on NAV-006 as a next generation anti-CD20 antibody that could improve the efficacy of parent RTX in NHL patients with high levels of CA125.