Abstract LB-414: Comparison of in vitro and in vivo immunologic responses in a prospective, randomized, single-blinded phase II trial evaluating the HER-2/neu peptide vaccines GP2 and AE37 in breast cancer patients
Authors: Sears Alan K. , Clifton Guy T. , Carmichael Mark G. , Van Echo David C. , Holmes Jarrod P. , Zacharia Athina , Jama Yusuf , Mursal Mohamed , Chiplis Anna , Mittendorf Elizabeth A. , Peoples George E. , Ponniah Sathibalan 
Published: August 2014

Abstract
BACKGROUND: We are conducting a prospective, randomized, single-blinded phase II trial evaluating the HER-2/neu peptide vaccines AE37 and GP2 in the adjuvant setting to prevent breast cancer recurrence. AE37 is the Ii-Key hybrid of the HER-2/neu peptide AE36 (HER-2/neu aa:776–790) and is capable of stimulating CD4+ helper T-cells with anti-tumor activity. GP2 is an HLA-A2+ -restricted immunogenic peptide from the HER-2/neu protein (HER-2/neu aa: 654–662) which is capable of stimulating CD8+ cytotoxic T-lymphocytes with the ability to recognize and destroy HER-2/neu-expressing tumor cells. Here we present data comparing the immunological profiles between these CD4 and CD8 eliciting vaccines
METHODS: Node positive or high-risk node negative breast cancer patients with any level of HER-2/neu expression rendered disease-free by standard treatments were enrolled. Patients were HLA-typed at enrollment. HLA-A2+ patients were placed in the GP2 arm and randomized to either GP2 + GM-CSF (immunoadjuvant) or GM-CSF alone. HLA-A2− patients were placed in the AE37 arm and randomized to either AE37 + GM-CSF or GM-CSF alone. Vaccinations were given in six monthly intradermal inoculations. In vitro (3H-thymidine proliferation for AE37, HLA-A2:immunoglobulin dimer for GP2) and in vivo (delayed-type hypersensitivity (DTH)) immune responses were measured before (R0), mid-series (R3), upon completion (R6), and at six (RC6) and twelve (RC12) months after completion of the vaccine series.
RESULTS: We have enrolled 247 patients (AE37=171, 87 vaccine and 84 control) (GP2=76, 41 vaccine and 35 control). Proliferative responses to both AE37 and AE36 were increased from baseline in the vaccine group at all time points (AE37: R0=0.98, R3=3.29, R6=3.38, RC6=3.64, RC12=3.68, p&lt;0.001; AE36: R0=0.95, R3=1.92, R6=2.12, RC6=2.18, RC12=1.80, p&lt;0.001) while they did not change for the control group. The population of circulating GP2-specific CD8+ T-cells measured in the dimer assay increased from baseline in the vaccine group at all time points (R0=1.00, R3=1.61, R6=1.85, RC6=1.95, RC12=1.93, p&lt;0.05) with no change in the control group. DTH responses increased in both AE37 and GP2 vaccinated patients from pre- to post-vaccination (AE37: 2.7 vs 30.2 mm, p&lt;0.001; AE36: 2.2 vs 16.3 mm, p&lt;0.001; GP2: 3.5 vs 29.4 mm, p&lt;0.001) while there was no significant change in the control group.
CONCLUSIONS: In a novel prospective, randomized, single-blinded phase II vaccine trial of the AE37 and GP2 peptide vaccines with a GM-CSF only control group, breast cancer patients vaccinated with either a CD4 or CD8 eliciting peptide vaccine exhibit high levels of HER-2/neu-specific in vitro and in vivo immune responses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-414. doi:10.1158/1538-7445.AM2011-LB-414