Priority Research Papers:
Tumor antigen CA125 suppresses antibody-dependent cellular cytotoxicity (ADCC) via direct antibody binding and suppressed Fc-γ receptor engagement
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James Bradford Kline1, Rina P. Kennedy1, Earl Albone1, Qimin Chao1, Shawn Fernando1, Jennifer M. McDonough1, Katherine Rybinski1, Wenquan Wang1, Elizabeth B. Somers1, Charles Schweizer1, Luigi Grasso1 and Nicholas C. Nicolaides1
1 Morphotek Inc., Exton, PA, USA
Nicholas C. Nicolaides, email:
Keywords: CA125, ADCC, farletuzumab, Fc-γ receptor, ovarian cancer
Received: May 15, 2017 Accepted: May 19, 2017 Published: July 07, 2017
Cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of tumor-shed antigen CA125/MUC16 on suppressing IgG1-mediated antibody-dependent cellular cytotoxicity (ADCC). This evidence stems from prespecified subgroup analysis of a Phase 3 clinical trial testing farletuzumab, a monoclonal antibody to folate receptor alpha, plus standard-of-care carboplatin-taxane chemotherapy in patients with recurrent platinum-sensitive ovarian cancer. Patients with low serum CA125 levels treated with farletuzumab demonstrated improvements in progression free survival (HR 0.49, p = 0.0028) and overall survival (HR 0.44, p = 0.0108) as compared to placebo. Farletuzumab’s pharmacologic activity is mediated in part through ADCC. Here we show that CA125 inhibits ADCC by directly binding to farletuzumab that in turn perturbs Fc-γ receptor engagement on effector cells.
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