Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Via Nizza, 52, 10126, Turin, Italy.
Department of Veterinary Sciences, University of Turin, Largo Braccini, 2, 10095, Grugliasco, Italy.
Cancer Immunol Immunother. 2019 Nov;68(11):1839-1853. doi: 10.1007/s00262-019-02360-6. Epub 2019 Jun 20.
Despite the significant progress in tumor prevention, early detection, diagnosis and treatment made over recent decades, cancer is still an enormous public health challenge all around the world, with the number of people affected increasing every year. A great deal of effort is therefore being devoted to the search for novel safe, effective and economically sustainable treatments for the growing population of neoplastic patients. One main obstacle to this process is the extremely low percentage of therapeutic approaches that, after successfully passing pre-clinical testing, actually demonstrate activity when finally tested in humans. This disappointing and expensive failure rate is partly due to the pre-clinical murine models used for in vivo testing, which cannot faithfully recapitulate the multifaceted nature and evolution of human malignancies. These features are better mirrored in natural disease models, i.e., companion animals affected by cancers. Herein, we discuss the relevance of spontaneous canine tumors for the evaluation of the safety and anti-tumor activity of novel therapeutic strategies before in-human trials, and present our experience in the development of a vaccine that targets chondroitin sulphate proteoglycan (CSPG)4 as an example of these comparative oncology studies.
尽管在肿瘤预防、早期检测、诊断和治疗方面取得了重大进展,但癌症仍然是全世界巨大的公共卫生挑战,每年受影响的人数都在增加。因此,人们正在努力寻找新的安全、有效和经济可持续的治疗方法,以满足不断增长的肿瘤患者群体的需求。这一过程的主要障碍之一是,在经过临床前测试成功后,实际上在最终在人体中进行测试时显示出活性的治疗方法的比例极低。这种令人失望且昂贵的失败率部分归因于用于体内测试的临床前小鼠模型,这些模型不能忠实地再现人类恶性肿瘤的多方面性质和演变。这些特征在自然疾病模型中得到了更好的体现,即患有癌症的伴侣动物。在此,我们讨论了自发性犬肿瘤对于评估新型治疗策略在人体试验前的安全性和抗肿瘤活性的相关性,并介绍了我们在开发针对硫酸软骨素蛋白聚糖 (CSPG)4 的疫苗方面的经验,以此作为这些比较肿瘤学研究的一个例子。