In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model.
Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse interleukin-12 elevated tumoral and serum levels of interferon-gamma and tumor necrosis factor-alpha, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.
Wang
C
C
Department of Pediatrics and Dermatology, Northwestern University Medical School, Chicago, Illinois, USA.
Quevedo
M E
ME
Lannutti
B J
BJ
Gordon
K B
KB
Guo
D
D
Sun
W
W
Paller
A S
AS
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006390:Hemangioendothelioma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics* / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma