Department of Oncology, Veterinary Specialty Center of the Hudson Valley, Wappingers Falls, NY, USA.
Vet Comp Oncol. 2014 Dec;12(4):310-8. doi: 10.1111/vco.12006. Epub 2012 Oct 25.
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.
基于直接接种质粒 DNA 的疫苗概念在小型啮齿动物物种中获得了初步的概念验证。然而,由于难以在大型动物物种中,尤其是在人体临床试验中证实其免疫原性和疗效,进一步的发展受到了阻碍。这些负面发现促使人们寻找互补技术,这些技术与皮内或肌肉内质粒 DNA 注射相结合,将导致更强大的传递、降低个体间的变异性、明确的临床疗效证据,并最终导致新疫苗产品获得市场批准。高压、无针设备作为质粒 DNA 传递的增强工具,最近已获得美国农业部的批准,用于治疗黑色素瘤的 Oncept™,这是一种针对酪氨酸酶的治疗性癌症疫苗。另一种改善质粒 DNA 传递的方法是电基因转移(EGT)。本文简要回顾了 DNA-EGT 的原理以及端粒酶逆转录酶疫苗在犬临床试验中的疗效证据,并为该技术在宠物动物中的更广泛应用提供了展望。