Electro‐gene‐transfer as a new tool for cancer immunotherapy in animals

Abstract

The concept of vaccines based on the direct inoculation of plasmid DNA gained initial proof-of-concept in small rodent species. Further development was hampered by the difficulty to confirm immunogenicity and efficacy in large animal species and, most importantly, in human clinical trials. These negative findings led to the search of complementary technologies which, in combination with intradermal or intramuscular plasmid DNA injection would result in more robust delivery, decreased interindividual variability, clear evidence of clinical efficacy and which would eventually lead to market approval of new vaccine products. The use of high-pressure, needleless devices as an enhancing tool for plasmid DNA delivery led to recent approval by USDA of Oncept™, a therapeutic cancer vaccine directed against tyrosinase for the therapy of melanoma in dogs. An alternative approach to improve plasmid DNA delivery is electro-gene-transfer (EGT). In this article, we briefly review the principles of DNA-EGT and the evidences for efficacy of a telomerase reverse transcriptase vaccine in a dog clinical trial, and provide perspectives for the use of this technology for broader applications in pet animals.

Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells

“…Classic vaccination with recombinant antigens or peptides as monotherapy gives little clinical benefit [ 1 , 7 ]. Genetic vaccines show better clinical efficacy [ 8 , 9 ], also in veterinary [ 10 , 11 ] and translational oncology [ 12 ]. Potency of DNA immunization was demonstrated in a variety of clinical applications [ 13 , 14 ].…”

Prolongation of survival of dogs with oral malignant melanoma treated byen blocsurgical resection and adjuvantCSPG4‐antigen electrovaccination

“…As CSPG4 is a self‐antigen with poor or no immunogenicity in autologous hosts, in this study we used a plasmid coding for the hCSPG4, that is characterized by 82% homology and 88% similarity in its amino‐acid sequence when compared with its canine counterpart (cCSPG4), in order to break immune tolerance. The addition of electroporation to DNA vaccine delivery (electrovaccination) further increases the vaccine immunogenicity and its therapeutic efficacy, and prolongs the duration of the immune response …”

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

“…Electrovaccination combines the advantages of DNA vaccination and electroporation. Specifically, the former is easy to handle, applicable to a broad population, safe, and induces both cellular and humoral immune responses, whereas the latter enhances the expression of the protein encoded by the immunizing DNA and prolongs the duration of the immune response (28,29).…”