Vaccination with the extracellular domain of p185neu prevents mammary tumor development in neu transgenic mice.
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.
Esserman
L J
LJ
UCSF/Mount Zion Medical Center, Department of Surgery, San Francisco, CA 94120, USA.
Lopez
T
T
Montes
R
R
Bald
L N
LN
Fendly
B M
BM
Campbell
M J
MJ
D016475:3T3 Cells; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology; D005260:Female; D018734:Genes, erbB-2 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D017434:Protein Structure, Tertiary; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases