The oncolytic effect of Canine Parvovirus ns1 gene and Chicken Anemia vp3 gene in naturally occurring cases of Canine Transmissible Venereal Tumor (CTVT) is being reported. Dogs suffering from CTVT (N = 18) were systematically randomized into three groups viz. A, B, and C (n = 6). Animals of the groups A, B, and C received 100 µg of the ns1 gene, vp3 gene, and ns1 + vp3 gene combination, respectively, for three weeks intratumorally at weekly intervals; results were normalized against base values before commencement of therapy and after complete remission that were taken as negative and positive controls, respectively. Initiation of oncolytic gene therapy arrested the further progression of the tumor but most of the animals in the study underwent incomplete remission, indicating incomplete activity of ns1 and vp3 genes. The oncolytic effect of the treatments was in the order ns1 > vp3 > ns1 + vp3.
Oncolysis was accompanied by decreased mitotic index and AgNOR count, and increased TUNEL positive cells and CD4+ lymphocyte counts. Our findings show that Canine Parvovirus ns1 may eventually find an important role as an oncolytic agent.Oncolytic viruses replicate preferentially in cancer cells and kill them at the end of the replication cycle. Live viruses were first used for the treatment of cancer more than a century ago. However, soon after its inception, the approach had to be abandoned due to problems of toxicity, development of antiviral immunity and risk of re-emergence of virulent viruses 1 . Lately, there has been a revival of scientific interest in the development of virus-based cancer therapeutics. Molecular biotechnology has allowed genetic engineering of viruses for enhanced selectivity towards tumor cells -an approach that was first demonstrated with Herpes Simplex virus type-1 (HSV-1) in an experimental glioma model 2 . Successively, several viruses with high oncolytic capacity have been identified as potential candidates for clinical applications. Chicken anemia virus and canine parvovirus are two such viruses that possess inherent oncolytic properties 3 . The chicken anemia viral protein (VP) 3, also termed apoptin, specifically, kills tumor cells while sparing normal cells. Upon expression in normal cells, apoptin is accumulated in the cytoplasm whereas in cancer cells, it is specifically targeted to the nucleus where it elicits its lethal effects 4 . Canine parvovirus-2 (CPV-2) is an extremely simple DNA virus that encodes one to two early products and a limited number of late structural proteins. It lacks mechanisms for inducing S phase and replicates only in proliferating host cells. This feature confers additional selectivity for killing rapidly growing cancer cells. The apoptosis-inducing activity of parvoviruses was mapped to the non-structural protein-1,-2 (ns1/ns2) of minute virus of mice (MVM) and ns1 of parvovirus B19 5 . Unlike apoptin, ns1 does not rely solely on apoptosis for its oncolytic effect.Biological similarities with humans make the dog an ideal comparative model system for study...