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Antibody Response against the c-erbB-2 Oncoprotein in Breast Carcinoma Patients¹

Divisions of Experimental Oncology E and Anatomical Pathology and Cytology; Istituto Nazionale per lo Studio e la Cura dei Tumori Via Venezian 1, 20133 Milan, Italy

Indirect immunofluorescence analysis of sera from breast carcinoma patients whose tumors were characterized for overexpression of the c-erbB-2 oncoprotein (p185^HER2) and for lympho-plasma cell infiltration, revealed no circulating antibodies specifically directed against the p185^HER2 molecule in the 20 samples tested, whereas supernatants of B-cell clones, derived from Epstein-Barr virus-transformed peripheral blood lymphocytes from 10 of these patients, contained such antibodies in 6 of the 7 c-erbB-2- and lympho-plasma cell infiltration-positive cases. The antibodies contained in two of the positive supernatants immunoprecipitated a M_r 185,000 molecule from oncoprotein-positive cell extracts that was identified as the oncoprotein in sequential immunoprecipitation experiments with anti-p185^HER2 monoclonal antibodies. No cells producing antibodies with a similar reactivity were obtained from Epstein-Barr virus-transformed peripheral blood lymphocytes from breast carcinoma patients with p185^HER2-negative tumors or from healthy donors. These data prove the existence of an antibody response specifically directed against the p185^HER2 oncoprotein in breast carcinoma patients that may represent an important effector mechanism in the control of c-erbB-2-overexpressing tumors.

¹ This work was partially supported by grants from the Associazione Italiana per la Ricerca sul Cancro and CNR-ACRO.

² To whom requests for reprints should be addressed.

Received 9/ 1/93. Accepted 11/ 1/93.

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