Dendritic cells transfected with interleukin-12 and pulsed with tumor extract inhibit growth of murine prostatic carcinoma in vivo

• Published in: The Prostate 2003-06, Vol.55 (4), p.292-298
• Main Authors: Zhang, Shaobo, Zeng, Guangyuan, Wilkes, David S., Reed, Gerry E., McGarry, Ronald C., Eble, John N., Cheng, Liang
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Antigens, Neoplasm - immunology; Antigens, Neoplasm - pharmacology; Cell Division - immunology; dendritic cells; Dendritic Cells - immunology; Flow Cytometry; gene therapy; Immunotherapy, Adoptive - methods; interleukin-12; Interleukin-12 - genetics; Interleukin-12 - immunology; Male; Mice; Mice, Inbred C57BL; prostate; Prostatic Neoplasms - genetics; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Transfection
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.10246

BACKGROUND The induction of anti‐tumor immune response by injection of dendritic cells loaded with specific antigen or transduced with genes encoding tumor‐specific antigens have been studied in animal models and have shown promising anti‐tumor effects. The impact of different routes of administration of dendritic cells on their anti‐tumor effects is uncertain. METHODS We examined the effect of injection of cloned dendritic cells, which were stably transfected with IL‐12 and exposed to an extract of murine RM‐9 prostate carcinoma cell antigens on tumor growth in vivo. The cloned dendritic cells were injected intramuscularly, subcutaneously, or intraperitoneally into C57BL/6 mice. Seven days later, the mice were inoculated subcutaneously with 100,000 RM‐9 cells. The sizes of the resulting tumors were measured every 3 days. RESULTS Compared with the wild type dendritic cells, the IL‐12‐transfected dendritic cells delayed tumor engraftment by 7 days (P = 0.04), and reduced tumor growth by up to 80% (P = 0.02). Among the three routes of injection, intramuscular injection was most effective. In contrast to wild type dendritic cells, IL‐12‐transfected dendritic cells induced infiltration of mononuclear cells into the tumors, and induced apoptosis and necrosis of tumor cells. Injection of IL‐12‐transfected dendritic cells also significantly delays tumor growth in the preexisting RM‐9 tumors. CONCLUSIONS We conclude that antigen‐exposed, IL‐12‐transfected dendritic cells have potential as an immunotherapy for prostate carcinoma. Routes of administration of dendritic cells are critical for maximal anti‐tumor effect. Prostate 55: 292–298, 2003. © 2003 Wiley‐Liss, Inc.