IL-12 based gene therapy in veterinary medicine

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.

Figure 1

Intratumoral EGT procedure in a dog with a mast cell tumor in the gluteal region.A: tumor before the procedure; B: intratumoral injection of IL-12 plasmid; C: delivery of electric pulses using plate electrodes with electric pulse generator Cliniporator® (Igea s.r.l., Italy); D: nodule immediately after the procedure. A marked paleness of the electroporated area compared to the surrounding tissue can be seen (arrow), due to transient reduction of the blood flow to the tissue, caused by occlusion of blood vessels during electroporation; E: tumor 10 days after therapy.

Figure 2

Mast cell tumor on the front leg of a dog, treated with a combination of ECT with cisplatin andIL-12EGT as part of an ongoing clinical study at our institution.A: a large ulcerated tumor nodule before therapy, B: one week after the procedure, massive necrosis of the treated area can be seen; C: one month after the procedure, a cytologically confirmed complete response was achieved.