Prevalence of high affinity naturally occurring IgG2 antibodies against human chorionic gonadotropin and its subunits in patients with ovarian cyst

Naturally occurring antibodies to tumour antigens are gaining interest as clinically important cancer biomarkers for early diagnosis, prognosis and for the development of anti-cancer therapeutics. The glycoprotein αβ heterodimer hormone human chorionic gonadotropin (hCG) and its β subunit (hCGβ) are produced by various cancers, and their increased serum levels correlate with poor prognosis. We have previously reported that patients with benign ovarian cysts, but not the malignant tumours, were characterized by augmented serum levels of naturally-occurring IgG antibodies to hCG and hCGβ. Here we further characterise these antibodies in patients with ovarian cysts. IgG and IgM antibody binding to whole hCG, hCGβ, hCGα, hCGβ C-terminal peptide (hCGβCTP), and the hCGβ core fragment (hCGβCF) were measured in the sera from 36 patients with ovarian cysts and 12 healthy non-pregnant women using a standard ELISA. IgG subclass usage and affinity was also determined together with cross-binding to whole hCG and its subunits of four selected commercial monoclonal antibodies generated against ovarian cyst mucins. Our results showed that 91.7% of the sera tested contained elevated IgG, but not IgM antibodies to one or several antigens, with an overwhelming prevalence of high affinity IgG2 indicating their binding to carbohydrate epitopes and possibly ovarian cyst mucins. Anti-mucin commercial antibody ab212418 (Abcam) produced against Gal1-3GalNAc, exhibited strong cross-binding to hCGαβ, hCGβ, hCGα and hCGβCTP. The protective anti-cancer potential of these antibodies will be further investigated and could lead to the development of novel treatment strategies for ovarian cancer