STUDIES ON THE AUTOLOGOUS HUMORAL IMMUNE RESPONSE TO OVARIAN CARCINOMA

• Main Author: LUTZ, PAULA MARCELLUS
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1981
• Subjects: Immunology
• ISBN: 9798204516564

Ovarian carcinoma, a leading cancer killer of women, is difficult to diagnose at early, curable stages. Associated markers have been described, but assays for their detection lack sensitivity and specificity for ovarian cancer; therefore, a serological test for early detection is still not a reality. However, there is good evidence for a cell-mediated immune response to the malignancy and indirect evidence for an associated antibody response. The purpose of this project was to evaluate the patient's humoral immune response to ovarian carcinoma. The objectives were to confirm the existence of tumor cell-surface immunoglobulins and to characterize these immunoglobulins more extensively; to isolate immune complexes from the ascites or tumor cell surfaces and characterize the physical properties of these complexes; to recover antibody activity from the complexes and define the specificity of the recovered antibody. Reports of serum factors which block cell-mediated immunity and levels of putative complexes which correlate well with tumor burden led to a hypothesis of a tumor-associated if not a tumor-specific humoral response. The presence of IgG, IgA, and IgM bound to cells in the ascites of ovarian cancer patients was confirmed using immunofluorescence. Differential staining techniques revealed the presence of inflammatory cells as well as tumor cells in the fluids. Polyethylene glycol precipitation and affinity chromatography on Protein A-Sepharose CL-4B was utilized to isolate putative complexes from ascites. Ultracentrifugation analyses of ascites showed no large MW IgG-containing complexes present (assessed by radial-immunodiffusion). Low levels of small complexes were noted, but at concentrations no greater than that found in a NHS pool. Clq is not bound by these complexes. Activity of antibody dissociated from the complexes was shown in an ('125)I-Staphylococcal Protein A binding assay, and specificity defined using cell absorption assays and polyacrylamide gel electrophoresis. Data indicate what appears to be autoreactivity directed against normal components of all cells with the possibility of a minor tumor-associated components. Such an autoimmune response has been reported in other malignancies; why it should be present is not known, but chemotherapy with resulting tissue damage may play a role.