Abstract
Abstract Tumors employ a variety of mechanisms to avoid host cellular and humoral immune responses. Recent findings have found that the tumor-produced MUC16/CA125 protein elicits humoral immunosuppressive effects on antibody-mediated tumor cell killing. This effect is facilitated via direct binding to SIGLEC regulatory receptors on natural killer (NK) cells as well as through direct binding to therapeutic antibodies that blocks Fc-γ-receptor and C1q antibody engagement, leading to suppressed antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) activities, respectively. We have engineered a human IgG1 Fc fusion protein, called NAV-005, that binds to CA125 with high affinity and blocks its binding to SIGLEC receptors and affected antibodies, thus enabling efficient humoral immune mediated tumor cell killing. NAV-005 is being developed as a novel therapeutic agent to treat humoral immuno-suppressed CA125 expressing cancers. Citation Format: Nicholas C. Nicolaides, Brad Kline, Luigi Grasso. Development of NAV-005, a humoral immuno-suppressor antagonist for the treatment of CA125-expressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1703.
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