Immunobiology of her-2/neu transgenic mice.

Abstract

Development of the mammary gland is controlled by hormones and many other growth factors. Hyperplasia and neoplasia are thus a likely consequence of alterations in their number and type, or the number and function of their receptors. p185neu, a member of the epidermal growth factor family, is coded by the ErbB-2 oncogene. It is expressed in the normal human breast, but overexpressed and associated with a poor prognosis in 15-30% of breast tumours. Employment of ErbB-2 sequences as vaccinal antigens to induce an immune rejection of such tumours is being investigated in several transgenic animal models. One of the most aggressive models of mammary p185neu-dependent carcinogenesis is that of BALB-neuT mice, which are transgenic for the rat transforming Her-2/neu oncogene (a homologue of the human ErbB-2 oncogene). The progression of their early neoplastic lesions can be prevented with both cellular and DNA vaccines coadjuvated by antiangiogenic and immunostimulatory molecules. This suggests that induction of a specific immune reaction against a tumor target antigen may provide a way of preventing the onset of tumours in subjects with a high genetic risk of developing cancer.