Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats.
OBJECTIVE
Interleukin-12 (IL- 12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered IL-12 in a malignant brain tumor model.


METHODS
After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9L gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription-polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells. The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma.


CONCLUSIONS
These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.
DiMeco
F
F
Department of Neurological Surgery, Chemical Engineering, Pathology, and Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Rhines
L D
LD
Hanes
J
J
Tyler
B M
BM
Brat
D
D
Torchiana
E
E
Guarnieri
M
M
Colombo
M P
MP
Pardoll
D M
DM
Finocchiaro
G
G
Brem
H
H
Olivi
A
A
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D015316:Genetic Therapy; D018316:Gliosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007156:Immunologic Memory / Q000235:genetics; D007167:Immunotherapy; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics*; D008297:Male; D009368:Neoplasm Transplantation; D019899:Paracrine Communication / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018664:Interleukin-12