The aim of this study was to investigate means of increasing the efficiency with which
cancer cell death following local
radiation therapy (RT) is translated into the generation of
tumor immunity since, if this were to be achieved, it would be expected to enhance the rates of disease-free recurrence and survival. Our investigations centered around the use of
interleukin-3 (IL-3), expressed intratumorally using an inducible adenoviral vector, to alter the immunogenicity of established murine TRAMP-C1
prostate cancer receiving a course of fractionated local RT (7 Gy per fraction per day for 5 days). Because high systemic levels of
IL-3 can be associated with toxicity, a
tetracycline-regulated gene delivery system was employed. The results show that while intratumoral
IL-3 expression or RT alone caused a modest delay in TRAMP-C1
tumor growth, the combination was synergistic with 50% of mice being cured and developing a long-term,
tumor-specific state of immunity. Immunological analyses performed on splenic lymphocytes demonstrated that, compared to RT or
IL-3 alone, combined treatment significantly increased the number of
tumor-specific IFN-gamma-secreting and cytotoxic T cells. The study demonstrates that
tetracycline-regulated
IL-3 gene expression within
tumors can enhance the immune response to
prostate cancer and this can augment the efficacy of a course of RT without additional side effects.