A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha.
A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.
Horton
H M
HM
Vical, Inc., 9373 Towne Centre Drive, Suite 100, San Diego, CA 92121, USA. hhorton@vical.com
Anderson
D
D
Hernandez
P
P
Barnhart
K M
KM
Norman
J A
JA
Parker
S E
SE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D007739:L Cells; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D010957:Plasmids / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured