Abstract LB-414: Comparison of <i>in vitro</i> and <i>in vivo</i> immunologic responses in a prospective, randomized, single-blinded phase II trial evaluating the HER-2/<i>neu</i> peptide vaccines GP2 and AE37 in breast cancer patients
Authors: Alan K. Sears, Guy T. Clifton, Mark G. Carmichael, David C. Van Echo, Jarrod P. Holmes, Athina Zacharia, Yusuf Jama, Mohamed Mursal, Anna Chiplis, Elizabeth A. Mittendorf, George E. Peoples, Sathibalan Ponniah
Journal: Cancer Research (2011)

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&amp;lt;0.001; AE36: R0=0.95, R3=1.92, R6=2.12, RC6=2.18, RC12=1.80, p&amp;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&amp;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&amp;lt;0.001; AE36: 2.2 vs 16.3 mm, p&amp;lt;0.001; GP2: 3.5 vs 29.4 mm, p&amp;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