Effect of a novel II-key hybrid HER2/neu peptide (AE37) vaccine with GM-CSF as compared to GM-CSF alone on levels of regulatory T-cell (Treg) populations.

Abstract

2565 Background: Regulatory T cells (Treg) inhibit effector T-cell function and prevent autoimmunity; they are recognized as obstacles to cancer immunotherapy. Tregs are predominantly CD4+, suggesting that MHC class II peptide vaccines may stimulate Tregs, decreasing vaccine efficacy. Additionally, results from recent trials have suggested that GM-CSF immunoadjuvant may decrease the efficacy of cancer vaccines or even be harmful. We addressed these issues in an ongoing phase II clinical trial in breast cancer (BCa) patients receiving the novel Ii-key MHC class II HER2/neu peptide vaccine (AE37). Methods: Disease-free, high-risk BCa patients enrolled after standard therapy and were randomized to 6 monthly inoculations of AE37+GM-CSF (peptide group; PA) or GM-CSF alone (adjuvant group; AA). Peripheral blood is drawn before, during, immediately after and 6 months after vaccination (R0, R3, R6, and RC6 respectively). Tregs were detected with CD4, CD25, CD127 and FoxP3 antibodies and flow cytometry. Patients are monitored for recurrence of BCa. Results: Of 150 post-vaccination patients, paired data are available in 57 (28 AA, 29 PA). CD4+ and CD8+ lymphocyte levels are similar in both groups and do not significantly change with vaccination. Treg (CD4+CD25hi) populations do not change in the AA (R0: 5.1±.3%; R3: 4.8±.3%; R6: 5.0±.3%; RC6: 5.2±.2%, p=NS) but decrease in the PA (R0: 5.1±.3%; R3: 4.5±.2%, p=0.004; R6: 4.7±.3%, p=NS; RC6: 4.3±.6%, p=0.01) with vaccination. Tregs as quantified by CD4+CD25hiCD127- cells also do not change in the AA but decrease in the PA (R0: 4.3±.3%; R3: 3.8±.2%, p=0.01; R6: 3.8±.3, p=NS; RC6: 3.8%±.7, p=0.04) with vaccination. Populations of CD4+FoxP3+ and CD25hiFoxP3+ cells do not significantly differ between groups or change with vaccination. At a median follow up of 13 mo., there have been 7.2% (6/83) recurrences in the AA and 2.9% (2/67) in the PA (p=0.30). Conclusions: The AE37 + GM-CSF vaccine decreases Tregs during and after completion of vaccination while GM-CSF alone does not alter Treg levels. This suggests that AE37 may allow the immune system to more effectively fight cancer and correlates with an observed decrease in recurrences. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigen Express