A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease

Mary 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1273-1282
Number of pages10
JournalCancer Prevention Research
Volume6
Issue number12
DOIs
Publication statusPublished - 2013 Dec 1

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Insulin-Like Growth Factor Binding Protein 2
Breast Diseases
Vaccines
Breast Neoplasms
Vaccination
Neoplasms
T-Lymphocytes
Immunization
Combined Vaccines
IGF Type 1 Receptor
Subunit Vaccines
Protein Transport
Growth
Transgenic Mice
Disease-Free Survival
Breast
Carcinoma
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. / Disis, Mary L.; Gad, Ekram; Herendeen, Daniel R.; Phan-Lai, Vy; Park, Kyong Hwa; Cecil, Denise L.; O'Meara, Megan M.; Treuting, Piper M.; Lubet, Ronald A.

In: Cancer Prevention Research, Vol. 6, No. 12, 01.12.2013, p. 1273-1282.

Research output: Contribution to journalArticle

Disis, ML, Gad, E, Herendeen, DR, Phan-Lai, V, Park, KH, Cecil, DL, O'Meara, MM, Treuting, PM & Lubet, RA 2013, 'A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease', Cancer Prevention Research, vol. 6, no. 12, pp. 1273-1282. https://doi.org/10.1158/1940-6207.CAPR-13-0182
Disis, Mary L. ; Gad, Ekram ; Herendeen, Daniel R. ; Phan-Lai, Vy ; Park, Kyong Hwa ; Cecil, Denise L. ; O'Meara, Megan M. ; Treuting, Piper M. ; Lubet, Ronald A. / A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. In: Cancer Prevention Research. 2013 ; Vol. 6, No. 12. pp. 1273-1282.
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