Cloning of Human Monoclonal Antibodies Associated with Medullary Ductal Carcinoma.

It is intended to identify and characterize newly expressed proteins neo-antigens which elicit plasma cell reactions in medullary and in non-medullary ductal carcinomas with circumscription and plasma cell infiltration. To accomplish this purpose, we exploit recently developed molecular procedures in a new application to derive antibodies from the tumor-infiltrating plasma cells, and then use these antibodies to retrieve the proteins whose new expression in the tumors induced the response. Ig sequencing of two patient MC samples revealed reiteration, supporting the presence of a focussed, specific immune response against an antigen by reactive plasma cells in the MC tumor. Additionally, phage Fab clones from these combinatorial phage libraries were shown to bind to HTB24 cells, the only available MC cell line, confirming cell surface expression of the putative neo-antigens on these cells. The neo-antigens will be identified by immunoprecipitation with reactive antibodies. Subsequently these proteins will be assesed for possible roles in the malignant prolifiration and as subjects for anti-breast cancer interventions.