A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer

A recombinant vaccinia virus encoding human prostate-specific antigen (rV-P SA) was administered as three consecutive monthly doses to 33 men with risi ng PSA levels after radical prostatectomy, radiation therapy, both, or meta static. disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7 ), and 2.65 x 10(8) plaque forming units. Ten patients who received the hig hest dose also received 250 mu g/m(2) granulocyte-macrophage colony-stimula ting factor (GM-CSF) as an immunostimulatory adjunct. No patient experience d any virus-related effects beyond grade I cutaneous toxicity. Pustule form ation and/or erythema occurred after the first dose in all 27 men who recei ved greater than or equal to 2.65 x 10(7) plaque forming units. GM-CSF admi nistration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or wit hout GM-CSF were stable for at least 6 months after primary immunization. N ine patients remained stable for 11-25 months; six of these remain progress ion free with stable PSA levels. Immunological studies demonstrated a speci fic T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is s afe and can elicit clinical and immune responses, and certain patients rema in without evidence of clinical progression for up to 21 months or longer.