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.

Efficient expression of bioactive murine IL12 as a self-processing P2A polypeptide driven by inflammation-regulated promoters in tumor cell lines

“…In this regard, a number of local gene therapy approaches have been undertaken in veterinary clinical oncology. 32 By employing viral and non-viral gene delivery methods local antitumor effects have been achieved in cats, horses, and dogs. They demonstrate that IL12-based gene therapy is an effective approach.…”

Electroporation-Based Technologies for Medicine: Principles, Applications, and Challenges

“…To date, reports on the successful use of IL-12 GET for treatment of sarcoids in horses and different primary tumors in dogs are available (128,129). In addition, one study describes the successful combination of ECT and GET for treatment of tumors in dogs (130).…”

Intracellular Tracking of Single-plasmid DNA Particles After Delivery by Electroporation

“…The transfer of plasmid DNA by the application of electric field pulses is a simple and widespread method. [1][2][3][4][5][6][7] It is an attractive approach for gene therapy as it is the most efficient among nonviral methods. [8][9][10] In contrast with virus-based transfection, DNA delivered by electroporation is not fully optimized with respect to overcoming cellular barriers such as the plasma membrane, cytoplasmic crowding, or the nuclear envelope.…”