Vaccination with the extracellular domain of p185 neu prevents mammary tumor development in neu transgenic mice

Abstract

The HER2/neu oncogene product, p185(HER2/neu), is overexpressed on the surface of many human breast cancers. Strains of transgenic mice have been developed that express the rat neu oncogene in mammary epithelial cells and develop spontaneous mammary tumors that overexpress p185neu. This model provides an ideal system for testing interventions to prevent tumor development. In this study, we immunized neu-transgenic mice with a vaccine consisting of the extracellular domain of p185neu (NeuECD). Immunized mice developed Neu-specific humoral immune responses, as measured by circulating anti-Neu antibodies in their sera, and cellular immune responses, as measured by lymphocyte proliferation to NeuECD in vitro. In addition, the subsequent development of mammary tumors was significantly lower in immunized mice than in controls and vaccine treatment was associated with a significant increase in median survival.

Biologic and therapeutic role of HER2 in cancer

“…Most data on the preventive potential of HER2 vaccines have come from studies in genetically predisposed animals transgenically expressing the rat HER2/neu proto-oncogene or its mutated activating form, and which are tolerant to self neu (De Vecchi et al, 1999). Different vaccination strategies include: rat HER-2/neu-positive allogeneic cells alone (Cefai et al, 1999) or in combination with interleukin-12 ; the extracellular domain of the rat oncoprotein (Esserman et al, 1999) or peptides derived from it (Dakappagari et al, 2000); and DNA plasmids encoding different fragments of activated rat neu gene or the HER2 full-length gene (Amici et al, 2000;Rovero et al, 2000;Pupa et al, 2001).…”

HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination

“…9 The antitumor immune responses induced by DNA vaccines could protect mice from challenge of HER-2/neu-positive tumor cells 10,11 and partially reduce tumor development in rat HER-2/neu-gene transgenic mice. [12][13][14] Insertion of interleukin (IL)-1b sequence 15 or co-administration of genetic adjuvants 16,17 or primeboost vaccination with plasmid DNA and adenovirus gene therapy 18 all induced enhanced antitumor immunity. However, these approaches still did not induce any therapeutic effects even with in vivo DNA electroporations.…”

Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

“…This neoplasm has been studied intensively, and recently new preventive measures and therapies emerged, including immunological and genetic treatments administered as adjuvant therapy after surgery, radiation, and chemotherapy. Biotherapy produced successful results in mice with mammary carcinoma, particularly with cellular vaccines (2), DNA vaccines (3,4), recombinant proteins (5), and adoptive immunotherapy (6).…”