Tumor regression induced by intratumoral injection of DNA coding for human interleukin 12 into melanoma metastases in gray horses.
Preclinical studies investigating new therapeutic principles against melanoma are presently being carried out in mouse models; however, these are not optimal. Here we describe a novel animal model using gray horses. These animals spontaneously develop metastatic melanoma that resembles human disease and is thus highly relevant for preclinical studies testing new immunotherapy protocols. We found that injection of plasmid DNA coding for the human cytokine interleukin 12 into established metastases induced significant regression in all 12 treated lesions in a total of 7 horses. Complete disappearance was observed in one treated lesion, with no recurrence after 6 months. No adverse events have been observed in any of the animals during and after treatment. These results demonstrate the effectiveness and safety of interleukin 12 encoding plasmid DNA therapy against established metastatic disease in a large animal model and serve as a basis for a clinical trial.
Heinzerling
L M
LM
Institute of Medical Virology, University of Zurich, Switzerland.
Feige
K
K
Rieder
S
S
Akens
M K
MK
Dummer
R
R
Stranzinger
G
G
Moelling
K
K
D000375:Aging; D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006736:Horses / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma