Abstract 1229: Pre-existing NY-ESO-1-specific T cell reactivity is associated with improved clinical outcome in castration resistant prostate cancer patients treated with Prostate GVAX and ipilimumab.
Authors: Stam Anita GM , Santegoets Saskia JAM , van den Eertwegh Alfons JM , Scheper Rik J. , Lougheed Sinéad M. , Gall Helen , Jooss Karin , Sacks Natalie , Harding Thomas , Hege Kristen , Lowy Israel , Gnjatic Sacha , Wolchok Jedd D. , Gerritsen Winald R. , de Gruijl Tanja D. 
Published: August 2014

Abstract
The effects of a GM-CSF-secreting allogeneic prostate cancer vaccine (Prostate GVAX) and the anti-CTLA4 antibody ipilimumab were investigated in a Phase I dose escalation/expansion trial of patients with metastatic castration resistant prostate cancer (van den Eertwegh et al, Lancet Oncology, 13: 509-17 2012). The GVAX and ipilimumab combination treatment led to PSA declines of more than 50% (Partial Response, PR) in 5 of 28 patients, PSA stabilizations (Stable Disease, SD) in 12 of 28 patients and disease progression (PD) in 11 of 28 patients. Regressing bone and lymph node metastases were observed in 2/5 PR patients. As an indication of tumor antigen-specific responsiveness we analyzed serologic and T cell responses against NY-ESO-1 before, during and after treatment. NY-ESO-1 seroreactivity (determined by ELISA) was observed in seven of 28 patients (25%). Five patients were seropositive at baseline and 2 became seropositive following treatment; no significant correlations were found with clinical benefit or survival. NY-ESO-1 T cell reactivity was determined in 19 patients by IFNγ ELISPOT after stimulation with a peptide pool of overlapping 20-mer peptides covering the immunodominant region aa121-180. NY-ESO-1-specific T cell responses were detected in 13 of 19 patients (68%) at any time before or during treatment. Increases in the frequency of NY-ESO-1 specific T cells following treatment were only observed in five of these (26%). A remarkably high number of nine out of 19 patients (47%) already exhibited NY-ESO-1-specific T cell reactivity before treatment. Interestingly, three of four (75%) PR patients displayed pre-existing frequencies of NY-ESO-1 T cells, whereas these cells were only detected in six of 15 SD/PD (40%) patients. Moreover, patients with pre-existing NY-ESO-1 T cell reactivity demonstrated a significantly prolonged overall survival (p=0.044, log-rank test). These data suggest that baseline NY-ESO-1 T cell reactivity may have predictive value for the clinical outcome of prostate GVAX and/or ipilimumab treatment.
Citation Format: Anita GM Stam, Saskia JAM Santegoets, Alfons JM van den Eertwegh, Rik J. Scheper, Sinéad M. Lougheed, Helen Gall, Karin Jooss, Natalie Sacks, Thomas Harding, Kristen Hege, Israel Lowy, Sacha Gnjatic, Jedd D. Wolchok, Winald R. Gerritsen, Tanja D. de Gruijl. Pre-existing NY-ESO-1-specific T cell reactivity is associated with improved clinical outcome in castration resistant prostate cancer patients treated with Prostate GVAX and ipilimumab. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1229. doi:10.1158/1538-7445.AM2013-1229