Tumor antigen CA125 suppresses antibody-dependent cellular cytotoxicity (ADCC) via direct antibody binding and suppressed Fc-γ receptor engagement

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...

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Bibliographic Details
Published in:Oncotarget 2017-08, Vol.8 (32), p.52045-52060
Main Authors: Kline, James Bradford, Kennedy, Rina P, Albone, Earl, Chao, Qimin, Fernando, Shawn, McDonough, Jennifer M, Rybinski, Katherine, Wang, Wenquan, Somers, Elizabeth B, Schweizer, Charles, Grasso, Luigi, Nicolaides, Nicholas C
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Language:English
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Priority Research Paper
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Summary: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, = 0.0028) and overall survival (HR 0.44, = 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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.19090