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Targets of Infiltrating B Cells in Medullary Breast Cancer

H. Burgwald, D.R. Burton, H.J. Ditzel

Medullary breast cancer is a subtype that accounts for approximately 5% of all breast cancers in humans. It is characterized by prominent lymphoplasmacytic cell infiltrates in the tumor periphery, and patients with medullary breast cancer have a more favorable prognosis than do patients with other types of breast cancers at a similar disease stage. The positive correlation between the intensity of lymphoid infiltration and patients' survival suggests that the immune system may be involved in restraining the spread of this type of breast cancer. The target of these lymphoplasmacytic cell infiltrates are therefore of great interest, because the information may have important implications for detection and treatment of not only medullary breast cancers but breast cancers in general. No restriction on the T-cell repertoire has been detected.

We have studied the B-cell infiltrates in medullary breast cancer to determine whether antibodies produced by the infiltrating cells react with an antigen directly or indirectly involved in the control of tumor growth. First, using a technique based on amplification of the VDJ region of the gene for the immunoglobulin heavy chain, we found B-cell oligoclonal predominance among tumor-infiltrating B cells. This finding suggests that certain B-cell clones are expanded, possibly in response to specific stimuli associated with the tumor. Second, we generated antibody phage display libraries from lymphoplasmacytic cell infiltrates from patients with medullary breast cancer and retrieved Fabs of monoclonal antibodies by selection on medullary breast cancer tissue. Characterization of the targets of these selected antibodies is ongoing.

PUBLICATIONS

Ditzel, H.J., Garrigues, U., Andersen, C.B., Larsen, M.K., Garrigues, H.J., Svejgaard, A., Hellström, I., Hellström, K.E., Jensenius, J.C. Modified cytokeratins expressed on the surface of carcinoma cells undergo endocytosis upon binding of human monoclonal antibody and its recombinant Fab fragment. Proc. Natl. Acad. Sci. U.S.A. 94:8110, 1997.

Tornoe, I., Tittlestad, I., Kejling, K., Erb, K., Ditzel, H.J., Jensenius, J.C. Pilot scale purification of human monoclonal IgM (COU-1) for clinical trials. J. Immunol. Methods 205:11, 1997.