To: Gulo who wrote (20 ) 10/17/2000 1:55:38 AM From: grayhairs Read Replies (1) | Respond to of 103 oncolyticsbiotech.com EVALUATION OF REOVIRUS THERAPY FOR SPONTANEOUSLY OCCURRING CANINE TUMORS D Szentimrey*, KL Norman†, MC Coffey‡, and BG Thompson‡; *-Rocky Mountain Surgery, Calgary, AB; †-University of Calgary, Calgary, AB; ‡-Oncolytics Biotech Inc., Calgary, AB. INTRODUCTION: It has been demonstrated that reovirus is capable of causing tumor regression in Ras mediated neoplasms in a number of animal models by a direct oncolytic effect. To evaluate if canine tumors were susceptible to reovirus oncolysis, tumor biopsies were taken from a variety of spontaneously occurring canine neoplasms, and cultured in vitro. These primary cultures were then exposed to reovirus and assessed for cytopathic response and viral replication. To investigate whether reovirus can mediate tumor regression or tumor clearing in large mammals, client owned canines of various breeds and sexes with histologically confirmed disease were treated with intralesional injections of reovirus. METHODS: Tumor biopsies were taken from a variety of cancer indications and cultured in vitro. These primary cultures were then exposed to reovirus and assessed for viral protein synthesis by [35S] methionine metabolic labelling. To evaluate whether the virus could promote in vivo tumor regression, client owned canines of varying breeds, body weights, and sexes with histologically confirmed malignancies were administered 3 intralesional injections of reovirus type 3 Dearing (1x1010 Plaque Forming Units (PFUs)). Animals were followed for a 2 to 3 week period followed by surgical resection of the tumor mass where possible. RESULTS: In vitro studies of canine tumor susceptibility to reovirus suggest that approximately two-thirds of tumors, regardless of origin, were susceptible to reovirus as measured by viral protein synthesis and cytopathic effect. In the in vivo model, the majority of animals demonstrated response as measured by either tumor clearing as confirmed by H/E staining or actual tumor regression. Additionally, a number of animals demonstrated regression of remote, untreated tumor masses, suggesting systemic spread of the virus. Importantly, no acute side effects were reported during the course of treatment. DISCUSSION: Although preliminary, these results suggest that reovirus is potentially a safe, broad spectrum therapeutic for the treatment of Ras mediated malignancies in canine companion animals. --------------------------------------------------------- Thread (if there's anybody still out there !!), Is the "bold type" statement above not a key and very significant observation ?? Does it not provide us with hope that reovirus therapy may ultimately be developed into an effective treatment for late stage metastasized cancers ?? Am I simply dreaming ?? Later, grayhairs