Biomarkers for Clinical Outcome of Combined Immunotherapy with Granulocyte-Macrophage Colony-Stimulating Factor-Tranduced Allogeneic Prostate Cancer Cells (GVAX) and Ipilimumab in Castration-Resistant Prostate Cancer Patients (CRPC)

In a phase-I dose escalation trial in patients (N = 28) with CRPC we showed that GVAX and ipilimumab had an acceptable safety profile (Lancet Oncology 2012). We observed tumor responses and prolonged survival. Patients had CRPC and were chemotherapy-naïve. They received bi-weekly GVAX for a 24 week period combined with monthly intravenous administrations of ipilimumab. Each cohort of 3 patients received an escalating dose of ipilimumab at 0·3, 1·0, 3·0 or 5·0 mg/kg. In an expansion cohort 16 patients were treated with GVAX and 3·0 mg/kg ipilimumab. Since the teratment can be accompanied by side-effects (colitis, hypophysitis), we looked for lymphoid and myeloid markers as well as antibody formation. We observed a significantly prolonged OS for patients with high pre-treatment frequencies of CD4 + CTLA-4 + , CD4 + PD-1 + , or differentiated CD8+ T cells, or low pre-treatment frequencies of differentiated CD4+ T cells or CD4 + CD25hiFoxP3+ regulatory T cells. In contrast, increased frequencies of granulocytic Myeloid-Derived Suppressor Cells and high pre-treatment frequencies of monocytic CD14 + HLA-DRlo/- MDSC were associated with reduced OS. Antibody formation against PSMA, NRP2, and PNPO was associated with prolonged survival and especially when multiple antibodies were detected.