ISOLATION OF A NEOANTIGEN IN MEDULLARY DUCTAL CARCINOMA

University Of Arizona, Tucson AZ

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Abstract

In this project, we seek to understand the unique immunobiology of medullary carcinoma (MC) of breast. These tumors are characterized by intense plasma cell (PC) infiltrates, unique in human tumor biology, that are associated with an impression of a more favorable natural course of MC tumors (and other PC-infiltrated breast tumors) after surgery-only therapy. It is our principal hypothesis that the marked infiltration of plasma cells and lymphoid elements reflects a local immune response against tumor that is etiologic in this apparently improved prognosis. This study will identify and characterize newly expressed proteins (neo-antigens) which elicit plasma cell reactions in medullary carcinomas (MC) of breast. We exploit reverse transcription of immunoglobulin transcripts followed by PCR (RT-PCR) and expression using phage display technology to derive antibodies from the tumor- infiltrating plasma cells. These antibodies will then be used to retrieve the proteins whose new expression in the tumors induced the PC response by screening cDNA expression libraries from MC. Antigen(s) retrieved will be analyzed for similarity to known proteins, expression in MC, normal tissues, and in other cancers, especially of the breast.