Clinical Trial Results of a HER2/<i>neu</i> (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients

Peoples, George E.; Gurney, Jennifer M; Hueman, Matthew T.; Woll, Mike M.; Ryan, Gayle B.; Storrer, Catherine E.; Fisher, Christine M.; Shriver, Craig D.; Ioannides, Constantin G.; Ponniah, Sathibalan

doi:10.1200/jco.2005.03.047

Cited by 217 publications

(155 citation statements)

References 25 publications

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“…Indeed, with breast cancer, most of these other approaches have been tried in animal models and in patients, some with highly encouraging results. [41][42][43][44][45][46][47][48][49] Although these results are promising, the next step is to identify a clinically feasible method to deliver this type of immunotherapy. Although live cells were used in our study, the use of inactivated tumor-APCs, transduced ex vivo with CIITA, costimulatory molecules (CD80 or CD86), and/or cytokines or chemokines, would be a more feasible approach and will be evaluated in our preclinical model.…”

Section: Discussionmentioning

confidence: 99%

Challenge with mammary tumor cells expressing MHC class II and CD80 prevents the development of spontaneously arising tumors in MMTV-neu transgenic mice

et al. 2006

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The HER-2/Neu oncogene has been implicated in human and mouse breast cancer. Indeed, transgenic MMTV-neu mice expressing this oncogene from the mammary tumor virus long terminal repeat develop spontaneous mammary tumors and die within 1 year of life. We have expressed the class II transactivator (CIITA) and/or the costimulatory molecule CD80 (B7.1) in a mammary carcinoma cell line (MCNeuA) derived from these mice. Class II transactivator directs the expression of MHC class II and the machinery for antigen processing and presentation by this pathway. When injected into MMTV-neu mice, tumor cells expressing CD80 or CD80 and CIITA, were rejected completely. In addition, following the rejection of dual expressing cells, 75% of the mice were protected against the development of subsequent spontaneous tumors. Cells expressing only CD80 or CIITA were not as effective as antitumor vaccines in preventing the development of spontaneous tumors. Thus, converting cancer cells into antigen presenting cells could represent an effective immunotherapy for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Challenge with mammary tumor cells expressing MHC class II and CD80 prevents the development of spontaneously arising tumors in MMTV-neu transgenic mice

et al. 2006

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“…NeuVax, which is composed of the human epidermal growth factor receptor 2 (HER2)-derived peptide E75 (nelipepimut-S) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunoadjuvant, appears to have clinical eicacy in early phase I/II trials [46,47]. It is now the only breast cancer vaccine being evaluated in a phase III trial [48,49]. Adoptive therapy with TILs is relatively active in melanoma patients [50].…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 99%

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

Dai¹

2017

Breast Cancer - From Biology to Medicine

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There are signiicant alterations in the tumor surrounding stromal cells in addition to the cancer cells in tumor microenvironment. Tumor cells can metastasize by acquiring the ability to escape immune control and surveillance. A decline in the ability of the immune cells to recognize and kill the tumor leads to tumor relapse or metastasis after primary treatment. Comprehensive review in this chapter will be conducted to further investigate into the mechanism of immune evasion in metastatic tumor microenvironment. The immune cells, stromal cells, extracellular matrix protein/component, and their interaction will be reviewed and summarized. Breast cancer has not been previously viewed as a particularly immunogenic type of tumor. Nevertheless, immune parameters have been increasingly studied in breast cancer, and accumulating data show that they are relevant for the development and progression of this tumor type. Consequently, immunotherapies of breast cancer are now tested in diferent clinical trials. The prospect of immunotherapy in metastatic breast cancer will be introduced. The importance of host-targeted modulation/therapy will be increased in addition to cancer-targeted strategies. We have to beter deine subpopulations of breast cancer patients to optimize the immunological way to overcome the cancer metastasis.

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“…In the first study, since E75 binds to the HLA-A2 allele, 29 HLA-A2 negative patients received a placebo and 24 HLA-A2 positive patients not previously treated using adjuvant trastuzumab therapy were vaccinated [68]. The vaccine was administered intradermally once a month for 6 months and the injected mixture consisted of different doses of E75 peptide (from 100 to 1,000 lg) in combination with 250 lg of GM-CSF.…”

Section: E75 Peptidementioning

confidence: 99%

Anti-HER2 vaccines: new prospects for breast cancer therapy

Ladjemi

Jacot

Chardès

et al. 2010

Cancer Immunol Immunother

118

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Each year, breast cancer accounts for more than 400,000 new cancer cases and more than 130,000 cancer deaths in Europe. Prognosis of nonmetastatic breast cancer patients is directly related to the extent of the disease, mainly nodal spreading and tumor size, and to the molecular profile, particularly HER2 over-expression. In patients with HER2-over-expressing tumors, different studies have shown cellular and/or humoral immune responses against HER2 associated with a lower tumor development at early stages of the disease. These findings have led to the hypothesis that the generation of an anti-HER2 immune response should protect patients from HER2-over-expressing tumor growth. Taken together with the clinical efficiency of trastuzumab-based anti-HER2 passive immunotherapy, these observations allowed to envisage various vaccine strategies against HER2. The induction of a stable and strong immunity by cancer vaccines is expected to lead to establishment of immune memory, thereby preventing tumor recurrence. However, an immunological tolerance against HER2 antigen exists representing a barrier to effective vaccination against this oncoprotein. As a consequence, the current challenge for vaccines is to find the best conditions to break this immunological tolerance. In this review, we will discuss the different anti-HER2 vaccine strategies currently developed; considering the strategies having reached the clinical phases as well as those still in preclinical development. The used antigen can be either composed of tumoral allogenic cells or autologous cells, or specific to HER2. It can be delivered by dendritic cells or in a DNA, peptidic or proteic form. Another area of research concerns the use of antiidiotypic antibodies mimicking HER2.

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Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients

Abstract: This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.

Cited by 217 publications

References 25 publications

Challenge with mammary tumor cells expressing MHC class II and CD80 prevents the development of spontaneously arising tumors in MMTV-neu transgenic mice

Challenge with mammary tumor cells expressing MHC class II and CD80 prevents the development of spontaneously arising tumors in MMTV-neu transgenic mice

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

Anti-HER2 vaccines: new prospects for breast cancer therapy

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