Peptide vaccine given with a toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors

Pilar Nava-Parada, Guido Forni, Keith L. Knutson, Larry R. Pease, Esteban Celis

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Our goal is to develop peptide vaccines that stimulate tumor antigen-specific T-cell responses against frequently found cancers. Previous work has shown that to generate effective T-cell responses, peptides have to be administered in combination with strong adjuvants such as Toll-like receptor agonists. However, most animal tumor model systems used to study peptide vaccines were not truly representative of malignant diseases in humans because they solely used transplantable tumor lines, and instead of true tumor antigens, they used highly immunogenic foreign proteins. Here, we describe a peptide vaccination strategy, which is highly effective in delaying or preventing the occurrence of spontaneous breast tumors. Transgenic female BALB-neuT mice that carry the activated rat HER-2/neu oncogene were vaccinated with a synthetic peptide from the rat HER-2/neu gene product, which represents an epitope for CTLs in combination with a Toll-like receptor agonist adjuvant. Our results show that to obtain tumor antigen-specific CTL responses and antitumor effects, the vaccine had to be administered repetitively, or the function of CD4/CD25 T regulatory cells had to be blocked with anti-CD25 antibody therapy. Mice that were vaccinated with this approach remained tumor-free or were able to control spontaneous tumor growth and exhibited long-lasting CTL responses, not only against the immunizing peptide but also against other peptides derived from rat HER-2/neu product (i.e., epitope spreading). These results suggest that similar strategies should be followed for conducting clinical studies in patients.

Original languageEnglish (US)
Pages (from-to)1326-1334
Number of pages9
JournalCancer Research
Volume67
Issue number3
DOIs
StatePublished - Feb 1 2007

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Subunit Vaccines
Toll-Like Receptors
Breast Neoplasms
Neoplasm Antigens
Peptides
erbB-2 Genes
Neoplasms
Epitopes
T-Lymphocytes
Therapeutics
Regulatory T-Lymphocytes
Oncogenes
Anti-Idiotypic Antibodies
Vaccination
Vaccines
Animal Models
Growth
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peptide vaccine given with a toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors. / Nava-Parada, Pilar; Forni, Guido; Knutson, Keith L.; Pease, Larry R.; Celis, Esteban.

In: Cancer Research, Vol. 67, No. 3, 01.02.2007, p. 1326-1334.

Research output: Contribution to journalArticle

Nava-Parada, Pilar ; Forni, Guido ; Knutson, Keith L. ; Pease, Larry R. ; Celis, Esteban. / Peptide vaccine given with a toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors. In: Cancer Research. 2007 ; Vol. 67, No. 3. pp. 1326-1334.
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