Cancer gene therapy in large animals

FINOCCHIARO, LILIANA M. E.; GLIKIN, GERARDO C.

New Gene Therapy and Cancer Research

Nova Science Publishers, Inc.

Lugar: New York, USA; Año: 2008; p. 279 - 292

Despite the important progress obtained in the treatment of many malignancies, the need to develop new treatments to fight cancer is compelling. Artificially created tumor models can be useful in the early stages of basic and applied research. The laboratory controlled disease, based on heterotopically grafted tumors in genetically identical small rodents that usually are young and healthy at the beginning of the trial, usually differs from human cancer in patients that spontaneously contracted the disease. Such patients are genetically heterogeneous and predominantly aged people whose immune system failed in fighting against the disease. These disparate situations can explain the failure of the translation to the field of some successful trials conducted in the laboratory. On the other hand, millions of pet dogs and cats will have cancer diagnosed every year. In many of those animals, the malignancy will look and behave as much as it would in humans, spreading to the same organs. In this context, spontaneous tumors appearing in large animals (especially companion animals) could offer a unique opportunity for both: (i) to develop new therapies for inherent pathologies and (ii) as models for human cancer biology and translational cancer therapeutics. With a potentially large population of cases for investigation, veterinary clinical trials can be completed faster and at significantly lower expense than similar human clinical trials. The successful trials could be easily translated to humans being benefited both humans and animal patients. This review discusses the outcomes of different assayed gene therapy approaches reported by many research centers on a variety of tumors such as melanoma, soft tissue sarcoma, fibrosarcoma and osteosarcoma, as well as our own experience on spontaneous canine and equine melanoma. The encouraging results obtained by means of these spontaneous cancer models in large animals supports not only their ready application in veterinary clinical oncology, but also as preclinical proof of concept and safety assay for forthcoming human gene therapy trials.