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Rapid generation of sustainable HER2-specific T cell immunity in HER2 breast cancer patients using a degenerate HLA class II epitope vaccine

Knutson, KL;Block, MS;Norton, N;Erskine, CL;Hobday, TJ;Dietz, AB;Padley, D;Gustafson, MP;Puglisi-Knutson, D;Mangskau, TK;Chumsri, S;Dueck, AC;Karyampudi, L;Wilson, G;Degnim, AC;

HER2+ breast cancer patients benefit from trastuzumab-containing regimens with improved survival. Adaptive immunity, including cytotoxic T cell and antibody immunity, is critical to clinical efficacy of trastuzumab. Since helper T cells are central to the activation of these antitumor effectors, we reason that HER2 patients treated with trastuzumab may benefit by administering vaccines that are designed to stimulate helper T cell immunity. We developed a degenerate HER2 epitope-based vaccine consisting of four HLA class II-restricted epitopes mixed with GM-CSF that should immunize most (84%) patients. The vaccine was tested in a phase I trial. Eligible women had resectable HER2+ breast cancer and had completed standard treatment prior to enrollment and were disease free. Patients were vaccinated monthly for six doses and monitored for safety and immunogenicity. Twenty-two subjects were enrolled and 20 completed all 6 vaccines. The vaccine was well tolerated. All patients were alive at analysis with a median follow-up of 2.3 years and only two experienced disease recurrence. The percent of patients that responded with augmented T cell immunity was high for each peptide ranging from 68-88%, which led to 90% of the patients generating T cells that recognized naturally-processed HER2 antigen. The vaccine also augmented HER2-specific antibody. Immunity was sustained in patients with little sign of diminishing at 2 years following the vaccination. Degenerate HLA-DR-based HER2 vaccines induce sustainable HER2-specific T cells and antibodies. Future studies, could evaluate whether vaccination during adjuvant treatment with trastuzumab-containing regimens improves patient outcomes. Copyright 2019, American Association for Cancer Research.