Abstract
The use of large animals as an experimental model for novel treatment techniques has many advantages over the use of laboratory animals, so veterinary medicine is becoming an increasingly important translational bridge between preclinical studies and human medicine. The results of preclinical studies show that gene therapy with therapeutic gene encoding interleukin-12 (IL-12) displays pronounced antitumor effects in various tumor models. A number of different studies employing this therapeutic plasmid, delivered by either viral or non-viral methods, have also been undertaken in veterinary oncology. In cats, adenoviral delivery into soft tissue sarcomas has been employed. In horses, naked plasmid DNA has been delivered by direct intratumoral injection into nodules of metastatic melanoma. In dogs, various types of tumors have been treated with either local or systemic IL-12 electrogene therapy. The results of these studies show that IL-12 based gene therapy elicits a good antitumor effect on spontaneously occurring tumors in large animals, while being safe and well tolerated by the animals. Hopefully, such results will lead to further investigation of this therapy in veterinary medicine and successful translation into human clinical trials.
Highlights
The concept of gene therapy involves the transfer of genetic material into target cells to overcome a genetic defect or to provide a protective or corrective function with the goal of curing a disease or improving the clinical status of a patient [1]
The results of this study indicate that intramuscular IL-12 Electrogene therapy (EGT) is a safe procedure in canine cancer patients, which can result in systemic shedding of IL-12 and possibly trigger an IFN-γ response, which could lead to prolonged survival of treated animals
A review of the literature shows that IL-12 based gene therapy may offer an effective new approach to cancer therapy in veterinary medicine
Summary
The concept of gene therapy involves the transfer of genetic material into target cells to overcome a genetic defect or to provide a protective or corrective function with the goal of curing a disease or improving the clinical status of a patient [1]. A similar expansion of local gene therapy to the systemic level was detected in another study on dogs with malignant melanoma, which received an intratumoral injection of lipid-complexed plasmid DNA encoding a bacterial superantigen and one of two cytokines, IL-2 or GM-CSF [53]. In 4/6 treated patients, serum concentrations of IL-12 and/or canine IFN-γ were detected in multiple blood samples (all three dogs with mast cell tumors and the dog with pulmonary histiocytic sarcoma), showing that the therapy elicited systemic release of the encoded transgene and an IFN-γ response In these four patients, even though the therapy did not have any effect on the volume of measurable tumor nodules, surprisingly long survival times after EGT were achieved, compared to survival times associated with specific tumor types from literature review. Dogs tolerated the procedure very well and did not show any clinical or laboratory indicators of renal, hepatic or systemic toxicity or immunosuppression, which are the most important adverse effects of recombinant IL-12 therapy [15]
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