Presence of aberrant tumor-reactive immunoglobulins in the circulation of patients with ovarian cancer

Objectives. Cancer patients generally exhibit circulating tumor-reactive im munoglobulins; however, these antibodies fail to eradicate tumors or preven t their progression, This study identifies and characterizes an aberrant tu mor-reactive IgG population present in women with ovarian cancer. Methods. In this pilot study, IgG was isolated from the sera of women with advanced-stage ovarian cancer (stages III and IV, n = 62) and age-matched f emale volunteers (n = 50) by affinity chromatography. These IgGs were chara cterized on the basis on their aberrant binding to concanavalin A affinity columns. Subsequently, the concanavalin A-binding moiety was localized foll owing IgG fragmentation, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and characterized by oligosaccharide profiling. Results. The level of concanavalin A-binding IgG in our control population was 8.9 +/- 2.9%, whereas in ovarian cancer patients, the level of concanav alin A-binding IgG was 38.8 +/- 7.4%. In the patients with ovarian cancer, 87.5 +/- 5.7% of the tumor-reactive IgG was demonstrated to be concanavalin A-binding. Based on oligosaccharide profiling of the fragmented concanaval in A-binding IgG, the aberrant lectin binding appeared to be the consequenc e of altered glycosylation of one of the two Fc chains. Conclusions. While our previous studies have identified the presence of cir culating Ige reactive with specific tumor-associated antigens and its assoc iation with poor prognosis, this report demonstrated the presence of an abe rrantly glycosylated IgG population in cancer patients. This altered IgG ap peared to be the primary class of tumor-reactive antibodies in these women. (C) 2001 Academic Press.