Abstract 3945: Antigen-specific immunity and regulation as predictive biomarkers for anti-tumor vaccination

Abstract

Abstract We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, PAP-specific proliferating and IFNγ-producing T cells developed in some patients, and persistent Th1-type immunity was associated with an increase in PSA doubling time. In the current study, we sought to determine if one or more measures of antigen-specific or antigen non-specific immunity present prior to treatment was associated with subsequent immune response as a possible predictive biomarker. Specifically, patients who had developed PAP-specific, IFNγ-secreting immune responses, detectable at least twice over one year after immunization, were defined as immune “responders”. The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells did not differ between the immune responder and non-responder groups. PAP-specific immune responses, detected as cytokine secretion following antigen stimulation of peripheral blood mononuclear cells in vitro, were detected in many patients pre-immunization. PAP-specific expression of granzyme B, IFNγ, and IL-6 was not significantly different between immune responding (n = 7) and non-responding patients (n = 23), however non-responder patients tended to have higher PAP-specific IL-10 production (p = 0.09). Using a trans vivo delayed-type hypersensitivity (DTH) assay to assess for antigen-specific immune regulation, responder patients tended to have preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen, a response previously demonstrated to be IL-35-mediated (p = 0.049). While the number of patients analyzed was low, these results suggest that different measures of antigen-specific regulation might help predict outcome from vaccination. These will be prospectively evaluated in an ongoing randomized, placebo-controlled, phase II trial evaluating this vaccine (NCT01341652). Citation Format: Laura E. Johnson, Brian M. Olson, Douglas G. McNeel. Antigen-specific immunity and regulation as predictive biomarkers for anti-tumor vaccination. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3945.