PSA-TRICOM (
PROSTVAC) is a novel vector-based
vaccine designed to generate a robust immune response against
prostate-specific antigen (PSA)-expressing
tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the
PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a ≥ 2-fold increase in PSA-specific T cells 4 weeks after
vaccine (median 5-fold increase) compared with pre-
vaccine, and 68% (19/28) of patients tested mounted post-
vaccine immune responses to
tumor-associated
antigens not present in the
vaccine (
antigen spreading). The PSA-specific immune responses observed 28 days after
vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for
influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the
tumor) and does not include
antigen spreading. Furthermore, although the entire PSA gene is the
vaccine, only one
epitope of PSA is evaluated in the T-cell responses. Because this therapeutic
vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that less than 0.6% of patients (2/349) tested have evidence of PSA antibody induction following
vaccine. This suggests that post-
vaccine PSA kinetics were not affected by PSA
antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes.