Block-Removed Immunoglobulin Technology to enhance rituximab effector function by counteracting CA125-mediated immunosuppression.

Rituximab (RTX) is a CD20-targeting antibody that is the standard-of-care for patients with non-Hodgkin Lymphoma (NHL) cases. RTX's mechanism of action includes complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Recent clinical evidence suggests that high serum levels of the tumor-produced mucin 16 (MUC16) and cancer antigen 125 (CA125) have a negative impact on the effectiveness of RTX clinical activity in up to 40% of patients with follicular lymphoma.

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 farletuzumab, a monoclonal antibody to folate receptor alpha, plus standard-of-care carboplatin-taxane chemotherapy in patients with recurrent platinum-sensitive ovarian cancer.