Twenty-four patients with locally advanced
prostate cancer (CaP) were enrolled in a phase I clinical trial using gene-based
immunotherapy. A functional
DNA-
lipid complex encoding the
interleukin 2 (IL-2) gene (
Leuvectin; Vical, San Diego, CA) was administered intraprostatically into the hypoecogenic
tumor lesion, using transrectal ultrasound guidance. Two groups of patients having locally advanced
tumors were enrolled to receive a treatment regimen composed of two serial intraprostatic
injections of the
IL-2 gene agent administered 1 week apart. The first groups of patients included radical
prostatectomy candidates who subsequently underwent surgery after the completion of the treatment regimen. The second group consisted of patients who had failed a prior
therapy. Prostate specimens of the treated areas were attained
after treatment and compared with the transrectal biopsies performed at baseline to assess for any responses.
IL-2 gene therapy was well tolerated, with no grade 3 or 4 toxic reactions occurring. The most commonly reported symptoms were mild
hematuria, transient rectal
bleeding, and perineal discomfort that are likely attributable to the injection itself. During the entire course of treatment, there were no significant changes in American Urologic Association (AUA) symptom scores, in hematologic disturbances,
electrolyte imbalances, or hepatic functions. Evidence of systemic immune activation was observed after
IL-2 gene therapy, based on an increase in the intensity of T cell infiltration seen on immunohistochemical analysis of tissue samples from the injected
tumor sites, and based on increased proliferation rates of peripheral blood lymphocytes that were cocultured with patient serum collected
after treatment. Furthermore, transient decreases in serum
prostate-specific antigen (PSA) (responders) were seen in 16 of 24 patients (67%) on day 1. Fourteen of the patients persisted in this decrease to day 8 (58%). In eight patients the PSA level rose (nonresponders). More patients (9 to 10) in the group that failed prior
therapy responded to the
IL-2 gene
injections (chi-square test, p = 0.04), and 6 of the 9 also had lower than baseline PSA levels at week 10
after treatment. To the best of our knowledge, this is the first clinical study of its kind aimed at exploring the role of IL-2-based gene therapy in CaP patients. This phase I trial demonstrated the safety of intraprostatic
Leuvectin injection, with transient PSA-based responses seen after
therapy.