Antitumor effects of recombinant BCG and interleukin-12 DNA vaccines on xenografted murine bladder cancer.
OBJECTIVE
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 C3H/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 C3H/HeN mice, with increased production of Th1-type cytokines, including interferon-gamma and IL-12. Treatment with multi-rBCG and/or mIL-12 in C3H/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.
Yu
Dah-Shyong
DS
Laboratory of Uro-oncology, Division of Urology, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Lee
Chi-Feng
CF
Hsieh
Dar-Shih
DS
Chang
Sun-Yran
SY
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D018274:Electroporation; D005260:Female; D005813:Genes, Synthetic; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D016233:Immunotherapy, Active; D018664:Interleukin-12 / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D014185:Transplantation, Isogeneic; D001749:Urinary Bladder Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D004269:DNA, Bacterial; D011994:Recombinant Proteins; D018664:Interleukin-12