title: 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.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guy T
authors.initials: GT
authors.lastname: Clifton
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Gall
authors.affiliation: Cancer Vaccine Development Program, Metis Foundation, San Antonio, TX, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
authors.affiliation: Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
keywords: Breast cancer; Cancer vaccine; E75; HER2; Nelipepimut-S