Interleukin 2 Gene Therapy for Prostate Cancer: Phase I Clinical Trial and Basic Biology
- 20 May 2001
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 12 (8) , 883-892
- https://doi.org/10.1089/104303401750195854
Abstract
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.Keywords
This publication has 8 references indexed in Scilit:
- Literary LunchCritical Survey, 1999
- Trends in the safety of high dose bolus interleukin-2 administration in patients with metastatic cancerCancer, 1998
- Intratumoral depot interleukin-2 therapy inhibits tumor growth in Dunning adenocarcinoma of the prostate implanted subcutaneously in ratsZeitschrift für Krebsforschung und Klinische Onkologie, 1997
- In vitro modulation of tumor progression-associated properties of hormone refractory prostate carcinoma cell lines by cytokinesCancer, 1996
- In vitro modulation of the invasive and metastatic potentials of human renal cell carcinoma by interleukin-2 and/or interferon-alpha gene transferCancer, 1994
- Expansion of Tumor-Infiltrating Lymphocytes from Human Tumors Using the T-Cell Growth Factors Interleukin-2 and Interleukin-4Journal of Immunotherapy, 1993
- Effects of Rectal Examination, Prostatic Massage, Ultrasonography and Needle Biopsy on Serum Prostate Specific Antigen LevelsJournal of Urology, 1992
- Tumor-infiltrating lymphocytes from nonrenal urological malignanciesCancer Immunology, Immunotherapy, 1990