We recently reported the clinical results of a Phase I trial combining ipilimumab with a vaccine containing transgenes for prostate-specific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castration-resistant prostate cancer.
Thirty patients were treated with escalating ipilimumab and a fixed dose of vaccine. Of 24 chemotherapy-naïve patients, 58 % had a PSA decline. Combination therapy did not exacerbate the immune-related adverse events associated with ipilimumab. Here, we present updated survival data and an evaluation of 36 immune cell subsets pre- and post-therapy. Peripheral blood mononuclear cells were collected before therapy, at 13 days and at 70 days post-initiation of therapy, and phenotyped by flow cytometry for the subsets of T cells, regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. Associations between overall survival (OS) and immune cell subsets prior to treatment, and the change in a given immune cell subset 70 days post-initiation of therapy, were evaluated. The median OS was 2.63 years (1.77-3.45). There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lower PD-1+Tim-3NEGCD4EM (P = 0.005, adjusted P = 0.010), higher PD-1NEGTim-3+CD8 (P = 0.002, adjusted P = 0.004), and a higher number of CTLA-4NEG Tregs (P = 0.005, adjusted P = 0.010). We also found that an increase in Tim-3+ natural killer cells post- versus pre-vaccination associated with longer OS (P = 0.0074, adjusted P = 0.015). These results should be considered as hypothesis generating and should be further evaluated in larger immunotherapy trials.
Written by:
Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J. Are you the author?
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD, 20892, USA.
Reference: Cancer Immunol Immunother. 2014 Feb 11. Epub ahead of print.
doi: 10.1007/s00262-014-1524-0
PubMed Abstract
PMID: 24514956
UroToday.com Prostate Cancer Immunotherapy Section
