Prognostic value and characterization of the ovarian cancer-specific antigen CA166-9

Abstract

COC166-9 is an ovarian cancer-specific monoclonal antibody, and COC166-9-based immunotherapy has been shown to possess killing effects against ovarian cancer cells in vitro and in vivo. However the antigen recognized by COC166-9 (COC166-9-Ag, CA166-9) has not been identified and the clinical significance of CA166-9 expression remains unknown. We found that CA166-9 was positive in 53.1% of ovarian cancer tissues. Expression of CA166-9 was strongly correlated with the cancer recurrence (P<0.001). Patients with positive CA166-9 had substantially shorter overall survival (P=0.026) and disease-free survival (P=0.002). CA166-9 was also shown to be an independent predictive factor for overall survival (HR=2.454, P=0.016) and disease-free survival (HR=2.331, P=0.021). We identified CA166-9 as human immunoglobulin γ-1 heavy chain constant region (IGHG1). Purified IGHG1 promoted proliferation, migration, and invasion of CA166-9-negative ovarian cancer HOC1A cells, whereas it had minimal effects on the phenotypes of CA166-9-positive ovarian cancer CAOV-3 cells. In addition, overexpression of IGHG1 enhanced migration of ovarian cancer cells. On the contrary, COC166-9 inhibited proliferation, migration, and invasion of CAOV-3 cells, but had no effects on HOC1A cells. Therefore, IGHG1 similarly to CA166-9, could play an important role in ovarian cancer development and may serve as a potential prognostic marker and a therapeutical target for ovarian cancer.

IGHG1 induces EMT in gastric cancer cells by regulating TGF-β/SMAD3 signaling pathway

“…Heavy and light chains of IgG have been detected in the cytoplasm of many human cancer cell lines [14]. The study found that IGHG1 was highly expressed in tumors such as ovarian cancer, and participates in pathological processes such as EMT, proliferation, apoptosis resistance, immune escape and metastasis of tumor cells [6,7]. Studies have also found that IGHG1 was significantly more expressed in pancreatic cancer tissues than in non-cancer tissues, IGHG1 downregulates the cytotoxic effects of NK cells by inhibiting the antigen-dependent cytotoxic function, leading to proliferation and immune escape of pancreatic cancer cells [15].…”

“…IGHG1 plays an important role in the occurrence and development of tumors. Its expression in ovarian cancer [6,7], pancreatic cancer [3], prostate cancer [8,9], papillary thyroid carcinoma [5] and other malignant epithelial tumors is significantly increased. It is involved in the pathological process of tumor cell EMT, proliferation, apoptosis resistance, immune escape and metastasis.…”

Localized Interleukin-12 for Cancer Immunotherapy

“…That these studies were successful in nude mice seems to imply a prominent role for NK cells in this model. CA166-9 is a cancer antigen that is expressed in about half of human ovarian cancers (91). A scFv of the 6B11 monoclonal antibody that binds to CA166-9 was fused to mIL-12 (92).…”

“…CA166-9 is a cancer antigen that is expressed in about half of human ovarian cancers ( 91 ). A scFv of the 6B11 monoclonal antibody that binds to CA166-9 was fused to mIL-12 ( 92 ).…”

IGHG1 promotes motility likely through epithelial-mesenchymal transition in ovarian cancer

“…Identifying unique antigens in malignancy and developing specific antibodies accordingly provide a critical therapeutical option (10). In the late 1980s, the antibody COC166-9 was found to be highly specific in OC (11), and experimental therapy showed that COC166-9 conjugated to cisplatin or adriamycin significantly inhibits xenograft tumor growth in immunocompromised mice (12). Further investigation revealed that immunoglobulin γ-1 heavy chain constant region (IGHG1) is the antigen target of COC166-9 and correlates with poor prognosis and recurrence in OC patients (13).…”