Antitumor effects of recombinant BCG and interleukin-12 DNA vaccines on xenografted murine bladder cancer

Abstract

Objectives To evaluate the antitumor effects of recombinant bacille Calmette-Guérin (BCG) DNA (multi-rBCG) and murine interleukin-12 DNA (mIL-12) vaccines on xenografted MBT-2 murine bladder tumors. Methods Treatment with combined multi-rBCG and mIL-12 was examined in syngeneic C 3H/HeN mice and athymic nude mice. The delivery efficiency of multi-rBCG expression was detected by flow cytometry. Inhibition of tumor growth was monitored, and antitumor effects were evaluated after one dose of electroporation immunogenetherapy, with measurement of cytokines and phenotyping of infiltrating lymphocytes in tumors. Results In vivo expression of multi-rBCG was efficient and reached a maximum on day 7 after electroporation. Treatment with multi-rBCG plus mIL-12 significantly inhibited tumor growth in C 3H/HeN mice, with increased production of Th1-type cytokines, including interferon-gamma and IL-12. Treatment with multi-rBCG and/or mIL-12 in C 3H/HeN mice induced infiltration of CD4+/CD8+ T cells and expansion of natural killer cells within tumors. By contrast, however, athymic nude mice treated in the same way showed no significant immune cells within tumors and died of the fast growing tumors. Conclusions Electroporation using multi-rBCG plus mIL-12 could be effective immunotherapy for existing bladder cancer. The antitumor effects correlated with the elicitation of Th1 lymphocytes and natural killer cell-mediated cytotoxic immune responses.