Purpose: This phase I-II study evaluated the safety, clinical activity and immunogenicity of an immunotherapy developed from human prostate cancer cell lines (PC-3 and LNCaP) modified to secrete granulocyte-macrophage colony-stimulating factor.
Materials and methods: Patients with noncastrate prostate cancer (19) with biochemical (prostate specific antigen) recurrence following prostatectomy or radiation therapy and no radiological evidence of metastasis were enrolled in the study. Patients were injected with an initial dose of 5 x 10(8) cells followed by 12 biweekly administrations of 1 x 10(8) cells. The adverse event profile, prostate specific antigen response, changes in prostate specific antigen kinetics and immunogenicity were assessed.
Results: Immunotherapy was well tolerated with no serious treatment related adverse events and no autoimmune reactions. A negative deflection in prostate specific antigen slope was observed in 84% of patients after treatment with a significant increase in median prostate specific antigen doubling time from 28.7 weeks before treatment to 57.1 weeks after treatment (p = 0.0095). Median time to prostate specific antigen progression was 9.7 months. Immunoblot analysis of patient serum demonstrated new or enhanced production of PC-3 or LNCaP reactive antibodies in 15 of 19 (79%) patients after immunotherapy. Induction of antibody responses reactive against PC-3 in general, and to the PC-3 associated filamin-B protein specifically, were positively associated with treatment associated changes in prostate specific antigen kinetics.
Conclusions: Granulocyte-macrophage colony-stimulating factor secreting cellular immunotherapy has a favorable toxicity profile with signals of clinical and immunological activity against hormone naïve prostate cancer. An association between immune response and prostate specific antigen changes was observed. Phase 3 trials in patients with advanced, metastatic, hormone refractory prostate cancer are under way.