title: A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease.
abstract: A multiantigen multipeptide vaccine, targeting proteins expressed in preinvasive breast lesions, can stimulate type I CD4(+) T cells which have been shown to be deficient in both patients with breast cancer and mice that develop mammary tumors. Transgenic mice (TgMMTV-neu) were immunized with a multiantigen peptide vaccine specific for neu, insulin-like growth factor-binding protein 2 and insulin-like growth factor receptor-I at a time when some of the animals already had preinvasive lesions (18 weeks of age). Although immunization with each individual antigen was partially effective in inhibiting tumor growth, immunization with the multiantigen vaccine was highly effective, blocking development of palpable lesions in 65% of mice and slowing tumor growth in the infrequent palpable tumors, which did arise. Protection was mediated by CD4(+) T cells, and the few slow-growing tumors that did develop demonstrated a significant increase in intratumoral CD8(+) T cells as compared with controls (P = 0.0007). We also combined the vaccine with agents that were, by themselves, partially effective inhibitors of tumor progression in this model; lapatinib and the RXR agonist bexarotene. Although the combination of lapatinib and vaccination performed similarly to vaccination alone (P = 0.735), bexarotene and vaccination significantly enhanced disease-free survival (P < 0.0001), and approximately 90% of the mice showed no pathologic evidence of carcinomas at one year. The vaccine also demonstrated significant clinical efficacy in an additional transgenic model of breast cancer (TgC3(I)-Tag). Chemoimmunoprevention combinations may be an effective approach to breast cancer prevention even when the vaccine is administered in the presence of subclinical disease.
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, 850 Republican Street, Box 358050, University of Washington, Seattle, WA 98109. ndisis@uw.edu.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Ekram
authors.initials: E
authors.lastname: Gad
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Herendeen
authors.forename: Vy Phan-
authors.initials: VP
authors.lastname: Lai
authors.forename: Kyong Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Denise L
authors.initials: DL
authors.lastname: Cecil
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Meara
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Lubet
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D000077610:Bexarotene; D005260:Female; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D000077341:Lapatinib; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D000077610:Bexarotene; D018971:Insulin-Like Growth Factor Binding Protein 2; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D013764:Tetrahydronaphthalenes; D022223:Vaccines, Subunit; C577903:IGFBP2 protein, human; C508053:ERBB2 protein, human