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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.
AuthorsMary L Disis, Ekram Gad, Daniel R Herendeen, Vy Phan- Lai, Kyong Hwa Park, Denise L Cecil, Megan M O'Meara, Piper M Treuting, Ronald A Lubet
JournalCancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 6 Issue 12 Pg. 1273-82 (Dec 2013) ISSN: 1940-6215 [Electronic] United States
PMID24154719 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • IGFBP2 protein, human
  • Insulin-Like Growth Factor Binding Protein 2
  • Quinazolines
  • Tetrahydronaphthalenes
  • Vaccines, Subunit
  • Lapatinib
  • Bexarotene
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Receptor, IGF Type 1
Topics
  • Adoptive Transfer
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology)
  • Bexarotene
  • Female
  • Insulin-Like Growth Factor Binding Protein 2 (antagonists & inhibitors, immunology)
  • Lapatinib
  • Lymphocytes, Tumor-Infiltrating (immunology, metabolism, pathology)
  • Mammary Neoplasms, Animal (immunology, pathology, prevention & control)
  • Mice
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • Precancerous Conditions (immunology, pathology, prevention & control)
  • Quinazolines (administration & dosage)
  • Receptor, ErbB-2 (antagonists & inhibitors, immunology)
  • Receptor, IGF Type 1 (antagonists & inhibitors, immunology)
  • T-Lymphocytes (immunology, metabolism, pathology)
  • Tetrahydronaphthalenes (administration & dosage)
  • Tumor Cells, Cultured
  • Vaccines, Subunit (therapeutic use)

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