Recombinant vaccinia-PSA [PROSTVAC] can induce a prostate-specific immune response in androgen-modulated human prostate cancer

Objectives. Prostate cancer recurrence, evidenced by rising prostate-specif ic antigen (PSA) levels after radical prostatectomy, is an increasingly pre valent clinical problem in need of new treatment options. Preclinical studi es have suggested that for tumors in general, settings of minimal cancer vo lume may be uniquely suitable for recombinant vaccine therapy targeting tum or-associated antigens. A clinical study was undertaken to evaluate the saf ety and biologic effects of vaccinia-PSA (PROSTVAC) administered to subject s with postprostatectomy recurrence of prostate cancer and to assess the fe asibility of interrupted androgen deprivation as a tool for modulating expr ession of the vaccine target antigen, as well as detecting vaccine bioactiv ity in vivo. Methods. A limited Phase I clinical trial was conducted to evaluate the saf ety and biologic effects of vaccinia-PSA administered in 6 patients with an drogen-modulated recurrence of prostate cancer after radical prostatectomy. End points included toxicity, serum PSA rise related to serum testosterone restoration, and immunologic effects measured by Western blot analysis for anti-PSA antibody induction. Results. Toxicity was minimal, and dose-limiting toxicity was not observed. Noteworthy variability in time required for testosterone restoration (afte r interruption of androgen deprivation therapy) was observed. One subject s howed continued undetectable serum PSA (less than 0.2 ng/mL) for over 8 mon ths after testosterone restoration, an interval longer than those reported in previous androgen deprivation interruption studies. Primary anti-PSA Ige antibody activity was induced after vaccinia-PSA immunization in subject, although such antibodies were detectable in several subjects at baseline. Conclusions. Interrupted androgen deprivation may be a useful tool for modu lating prostate cancer bioactivity in clinical trials developing novel biol ogic therapies. Immune responses against PSA may be present among some pati ents with prostate cancer at baseline and may be induced in others through vaccinia-PSA immunization. (C) 1999, Elsevier Science Inc. All rights reser ved.