www.acvim.org: go to Denver Conference, Research Abstracts, # 82...
82 GENETICALLY MODIFIED SALMONELLA FOR CANINE CANCER: A PHASE I STUDY. EG MacEwen 1 ,D Thamm 1 ,ID Kurzman 1 ,M Sznol 2 ,Z Li 2 ,I King 2 , 1 University of Wisconsin-Madison, WI. 2 Vion Pharmaceuticals Inc, New Haven, CT.
An attenuated Salmonella typhimurium (VNP20009) was generated by deletions in the msbB and purI genes. VNP20009 is unable to produce wild type lipopolysaccharides or to survive without an external source of purines. VNP20009 has been shown to preferentially accumulate and proliferate in tumors in immunologically intact and immune deficient mice without toxicity. Preclinical studies in murine tumor models show antitumor activity in a variety of tumors. The purpose of this Phase I study was to determine dose-limiting toxicity (DLT), confirm VNP20009 tumor targeting, and potential therapeutic activity in dogs with various measurable tumors. All dogs were clinically staged using standard methods. Tumor biopsies were obtained prior to and 7 days following the first treatment. VNP20009 was detected using bacterial culture and PCR using day 7 tumor biopsy material. Following treatments, dogs were monitored for clinical, hematological, and biochemical toxicity. Tumor response (CR, PR, SD, PD) was evaluated at each
visit. Dogs demonstrating a response were continued on treatment for at least 8 weeks. Treatments were discontinued in dogs showing PD.
Fourteen dogs were entered into this trial. Dogs received VNP20009 IV over 30 mins in doses ranging from 1.5 x 10 5 to 5 x 10 6 cfu/ kg. Mild fever occurred 2-4 hours after the infusion. VNP20009 has been detected in 4 of 8 tumor samples tested to date. No significant hematological or biochemical toxicities were encountered. One dog developed a protein-losing nephropathy histologically consistent with membranoproliferative glomerulonephropathy.
A durable CR was detected in one dog with a metastatic melanoma, 3 PRs (local tumor only) were seen in a rhabdomyosarcomas, melanoma, and an anaplastic carcinoma. Four dogs had SD (> 8 weeks) and 5 had PD. The results of this early phase I study indicate that VNP20009 is relatively safe at these doses. Furthermore, the antitumor responses noted are significant and additional clinical studies are currently underway.
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Priceton is not involved with VION,IMO. The science came out and the donation went to YALE! (which is also in New Haven).
Jim |
