Clinical Development of the E75 Vaccine in Breast Cancer

Abstract

E75 is an immunogenic peptide derived from the human epidermal growth factor receptor 2 (HER2) protein. A large amount of preclinical work evaluated the immunogenicity of E75, after which phase I trials investigated using E75 mixed with an immunoadjuvant as a vaccine. Those studies showed the vaccine to be safe and capable of stimulating an antigen-specific immune response. Subsequent to that, our group conducted trials evaluating E75 + granulocyte macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting. The studies enrolled node-positive and high-risk node-negative breast cancer patients, with the goal being to determine if vaccination could decrease the recurrence risk. The studies included 187 evaluable patients: 108 vaccinated ones and 79 controls. The 5-year disease-free survival for the vaccinated patients was 89.7% compared to 80.2% for the control patients, a 48% reduction in relative risk of recurrence. Based on these data, E75 + GM-CSF, now known as NeuVax™, is being evaluated in a phase III trial. In this article, we review preclinical data and results of the early-phase trials and provide an update on the ongoing phase III study. We also present additional strategies for employing the vaccine to be included as a component of combination immunotherapy as well as in the setting of ductal carcinoma in situ as an initial step towards primary prevention.

Human Mast Cells From Adipose Tissue Target and Induce Apoptosis of Breast Cancer Cells

“…TNF-α is an anti-cancer agent shown to suppress tumor cell proliferation, induce tumor regression, and used as an adjuvant that enhances the anti-cancer effect of chemotherapeutic agents (61–63). GM-CSF is also being investigated as an anti-breast cancer therapeutic, including its use in combination strategies with other immunotherapies (21, 64–67). There are over 50 clinical trials completed or underway examining the beneficial clinical effects of GM-CSF (www.clinicaltrials.gov).…”

HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development

“…Through the ADCC mechanism, trastuzumab-coated tumor antigens are released from tumor cells and taken up by DCs and presented on MHC class I molecules. Therefore, trastuzumab in combination with active immunotherapy, led to the greater expansion of peptide specific CTLs and higher cytotoxicity via enhancement of uptake and cross presentation of HER2 specific epitopes by DCs (Clifton et al 2016).…”

Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells

“…The first therapeutic DC vaccine, Sipuleucel-T (Provenge ® ), generated from autologous peripheral blood mononuclear cells pulsed with a prostatic acid phosphatase–GM-CSF recombinant fusion protein, [23] was approved for treatment of metastatic castration-resistant prostate cancer by the U.S. Food and Drug Administration (FDA) in 2010. A once promising non-DC vaccine, nelipepimut-S (E75) vaccine (NeuVax ™ ), for human epidermal growth factor receptor 2 (HER2) + breast cancer that contains the E75 antigen peptide mixed with the adjuvant, granulocyte-macrophage colony-stimulating factor (GM-CSF), [24, 25] was recently tested in a Phase III clinical trial, sponsored by Galena Biopharma, Inc.. However, the clinical trial was discontinued based on negative data from a planned safety and futility interim analysis.…”