Working towards the development of vaccines for the treatment and prevention of early breast cancer

Robert E. Roses, Min Xu, Shuwen Xu, Ursula Koldovsky, Gilsoo Son, Gary K. Koski, Brian J. Czerniecki

Research output: Contribution to journalReview article

Abstract

Recent studies of immune responses to pathogens have identified pathogen-associated molecular patterns (PAMPs) recognized by the innate immune system through specialized receptors called toll-like receptors (TLRs). Signaling through these receptors initiates robust immune responses. By exploiting TLR signaling pathways, immunity to tumor-associated antigens may be generated. Many tumor-associated antigens are involved in the regulation of tumor phenotype or carcinogenesis. Immune targeting of these antigens may either alter the tumor phenotype, yielding a more treatable tumor, or eradicate early tumor stem cells preventing tumor formation. The oncoprotein HER-2/neu, which is over-expressed in a significant number of pre-malignant breast lesions of ductal carcinoma in situ (DCIS), may provide such a target. Immune responses directed against HER-2/neu may eliminate the disease, make tumors more amenable to anti-estrogen therapy, or prevent escape of hormone-resistant tumor phenotypes. Effective breast cancer prevention in preclinical studies utilizing HER-2/neu transgenic murine models has stimulated interest in, and optimism regarding, protective breast cancer vaccines in humans. Induction of anti-HER-2/neu T cell (CD4+ and CD8+) and B cell responses has been demonstrated in an ongoing clinical study targeting HER-2/neu using a TLR agonist stimulated dendritic cell (DC) vaccine. Moreover, these vaccinations lead to reductions in both HER-2/ neu expression and extent of DCIS. HER-2/neu expression and aromatase activity have recently been linked through the intermediary cyclooxygenase 2 (COX2). This convergence between growth factor and hormone mediated pathways reinforces the notion that a significant number of breast cancers may be prevented through effective immune targeting of HER-2/neu. As progress is made in the development of vaccines for breast cancer prevention, the contributions of immune-mediated effector and inhibitory mechanisms to the pathogenesis of HER-2/neu over-expressing breast cancers will need to be better understood.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalCurrent Cancer Therapy Reviews
Volume3
Issue number2
DOIs
Publication statusPublished - 2007 May

Keywords

  • Ductal carcinoma in situ
  • EGFR family
  • Regulatory T Cells
  • Trastuzumab
  • Tumor Antigen

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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