EXISTENT T-CELL AND ANTIBODY IMMUNITY TO HER-2 NEU PROTEIN IN PATIENTS WITH BREAST-CANCER

The HER-2/neu protooncogene is amplified and overexpressed in 20-40% o f invasive breast cancers. HER-2/neu protein overexpression is associa ted with aggressive disease and is an independent predictor of poor pr ognosis in several subsets of patients. The protein may also be relate d to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be p ossible to develop specific T-cell therapy directed against proteins i nvolved in malignant transformation. One question is whether normal pr oteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/ neu-positive breast cancers have both existent CD4+ helper/inducer T-c ell immunity and antibody-mediated immunity to HER-2/neu protein. Init ial studies performed on 20 premenopausal breast cancer patients ident ified antibodies to HER-2/neu in 11 individuals. Similar antibody resp onses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a hu moral immune response this patient had evidence of a significant proli ferative T-cell response to the HER-2/neu protein and peptides. Simila r T-cell responses have been detected in additional patients. It has b een assumed that patients would be immunologically tolerant to HER-2/n eu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoi mmunity. The current data support the notion that HER-2/neu-specific i mmunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune su rveillance and cancer progression.