Breast cancer patients have different levels of endogenous CD8 T cells capable of recognizing a HER2/neu peptide (E75) used as a cancer vaccine in clinical trials

1860 Introduction: We are currently conducting clinical trials with the HER2/ neu E75 peptide vaccine in clinically disease-free node-positive (NP) and node-negative (NN) breast cancer (BrCa) patients. Administration of the E75 peptide with GM-CSF stimulates clonal expansion of E75-specific CD8 T cells. The purpose of this study is to determine the levels of pre-existing immunity to E75 in BrCa patients. Methods: Pre-vaccination peripheral blood samples were collected from a total of 63 (25 NP and 38 NN) BrCa patients. HLA-A2:Ig dimer molecules were loaded with the HER2/ neu peptide E75 and were used with anti-TcR and anti-CD8 antibodies to stain peripheral blood leukocytes immediately ex vivo. Samples were analyzed by flow cytometry and dimer+, E75-specific T cells reported as % of total CD8 + cells. Results: Both NP (60%) and NN (44.7%) BrCa patients have pre-existing immunity to E75 peptide. Levels of E75-specific CD8 T cells were higher in the NP group compared to the NN group (0.8% [range 0-2.6%] vs. 0.43% [range 0-3.28%], P=0.04). Compared to NN patients, NP patients also had larger tumors (40% ≥T2 vs. 13%, P=0.025) and were higher grade (52% grade 3 vs. 26%, P neu overexpression. Thirteen (21%) of patients had very high levels of pre-exisiting immunity (defined as E75-specific T cells >1%). This group with high dimer levels had more NP patients (76.9 vs. 30%, P=0.01), more patients with primary tumor ≥T2 (53.8% vs. 18%, P=0.01) and fewer patients that exhibited HER2/ neu overexpression (7.7% vs. 39.5%, P=0.05). Conclusions : We demonstrate evidence of pre-existing immunity to the E75 peptide in disease-free NP and NN BrCa patients. NP patients have greater levels of specific immunity than NN patients. Increased immunity in the NP group may be due to increased antigenic exposure from the larger tumors, positive lymph nodes, and higher grade tumors in this group. More NP patients received chemotherapy, therefore, the higher level of dimer may also be explained by decreased regulatory T cells post-chemotherapy. As the level of E75-specific T cells increased, HER2/ neu overexpression decreased, implying a degree of protective immunity conferred by the presence of specific HER2/ neu immunity.