In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma.
Interleukin 12 (IL-12) isa cytokine that promotesan antitumor Th1-type pattern of differentiation in mature naïveT cells. Despite its therapeutic success in multiple animal models of cancer, the utility of systemically administered recombinant cytokine has been limited by its toxicity. This has encouraged the development of local IL-12 delivery systems through gene transfer. To determine the effect of local adenoviral delivery of IL- 12 on glioma immunogenicity, mice bearing GL-26 gliomas in the right corpus striatum were treated with direct intratumoral administration of AdmIL-12, AdLacZ, or normal saline. Survival was significantly prolonged in AdmIL-12-treated animals and immunohistochemistry demonstrated robust CD4+ and CD8+ T-cell infiltration in these mice compared to the two control groups. Glioma-infiltrating T lymphocytes from mice that received AdmIL-12 also demonstrated relatively increased, albeit statistically nonsignificant tumor killing. Based on IL-12's known ability to enhance Th1-type cytotoxic antitumor immune responses, we postulate our findings to be a result of localized induction of tumor immunity.
Liu
Yunhui
Y
Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center Los Angeles, California 90048, USA.
Ehtesham
Moneeb
M
Samoto
Ken
K
Wheeler
Christopher J
CJ
Thompson
Reid C
RC
Villarreal
Luis P
LP
Black
Keith L
KL
Yu
John S
JS
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D018664:Interleukin-12 / Q000235:genetics*; D007763:Lac Operon / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018664:Interleukin-12