Dendritic cells transfected with interleukin-12 and pulsed with tumor extract inhibit growth of murine prostatic carcinoma in vivo.
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.
Zhang
Shaobo
S
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Zeng
Guangyuan
G
Wilkes
David S
DS
Reed
Gerry E
GE
McGarry
Ronald C
RC
Eble
John N
JN
Cheng
Liang
L
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014162:Transfection
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018664:Interleukin-12