Abstract LB-130: Immune reconstitution after chemotherapy correlates with increased in vitro immune response in breast cancer patients undergoing peptide vaccine therapy
Authors: Vreeland Timothy J. , Dabney Raetasha S. , Hale Diane F. , Sears Alan K. , Clifton Guy T. , Zacharia Athina , Jama Yusuf , Chiplis Anna , Mursal Mohamed , Shumway Nathan M. , Patil Ritesh , Holmes Jarrod P. , Mittendorf Elizabeth A. , Peoples George E. , Ponniah Sathibalan 
Published: August 2012

Abstract
Introduction: We are conducting a Phase II clinical trial of 2 HER2 peptide vaccines, GP2 (MHC Class I restricted) and AE37 (MHC Class II restricted), for the prevention of breast cancer (BCa) recurrence in disease-free, high risk patients (pts). We present analysis of T cell populations in trial patients at the time of enrollment and differences based on time since chemotherapy. We describe a “reconstitution” of the immune system after immunosuppressive chemotherapy. Methods: After completion of standard therapy, disease-free, BCa pts were enrolled. Demographic data was collected. Blood was collected prior to administration of their first vaccine. Peripheral blood mononuclear cells from 50 pts were isolated and evaluated for CD8+, CD4+CD8+, CD4-CD8- and CD4+ T cell populations. T cell proliferation responses were measured in patients of both arms of the trial; generically with FluM-specific CD8 cells (HLA-A2:Ig dimer assay) in the GP2 arm (n=58), and then with proliferation response to AE36 and AE37 in the AE37 arm (n=85). Linear regression analyses evaluated the relationship between time from chemotherapy and each T cell population. Immune responses of pts enrolled less than one year from chemotherapy (&lt;1yr group) were then compared with those enrolled more than one year from chemotherapy (&gt;1yr group) using a t-test. Results: Chemotherapy regimens were determined by the treating oncologist and consisted primarily of anthracycline-based regimens with a taxane. Regression analysis revealed a significant correlation between time from chemotherapy and both CD4+ and CD8+ Tcell counts (R= .433, p=0.015 and R=.439, p=.014, respectively). Total T cell, CD4-CD8- and CD4+CD8+ populations, however, did not significantly correlate with increased time from chemotherapy (R=.28, p=0.128, R=.068, p=.715 and R=.058, p=.755, repectively). Comparison between the &lt;1yr group and the &gt;1yr group in the GP2 arm (n=43 and n=15) for FluM-specific CD8 cells revealed a non-significant increase in immune response in the &gt;1yr group (2.74 vs 3.57, p=0.15). A similar comparison in the AE37 arm (n=56 &lt;1yr, n=29 &gt;1yr) revealed increased proliferation in the &gt;1yr group (AE36: 1110 vs 2167, p=0.034, AE37: 983 vs 2179, p=0.001). There were no significant differences between the &gt;1yr and &lt;1yr groups of either arm with respect to AJCC stage, HER2 status, or ER/PR status. Conclusion: Immune reconstitution is emerging as an important concept in the care of cancer pts, especially in immunotherapy, where enhancing a pts’ immune response is the key to success. We have shown that increased time from chemotherapy correlates with reconstitution of the immune system, manifest by increased CD8+ and CD4+ T cell counts and increased in vitro immune responses. Future analysis will determine if increased immune reconstitution, portends a better response to cancer vaccines and improved outcomes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-130. doi:1538-7445.AM2012-LB-130