Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation
| Autor: | Richard R. Dubielzig, David M. Vail, Ivan King, Ilene D. Kurzman, Mario Sznol, Douglas H. Thamm, Zujin Li, E. Gregory MacEwen |
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| Rok vydání: | 2005 |
| Předmět: |
Diarrhea
Male Salmonella typhimurium Cancer Research medicine.medical_specialty Fever Vomiting Context (language use) Pharmacology Vaccines Attenuated Dogs Neoplasms medicine Animals Dog Diseases Dose-Response Relationship Drug business.industry Genetically modified organism Bacterial vaccine Dose–response relationship Treatment Outcome Oncology Bacterial Vaccines Toxicity Immunology Systemic administration Female Histopathology medicine.symptom business |
| Zdroj: | Clinical Cancer Research. 11:4827-4834 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-04-2510 |
| Popis: | Purpose: Genetically modified bacteria are a potentially powerful anticancer therapy due to their tumor targeting capacity, inherent antitumor activity, and ability to serve as efficient vectors for gene delivery. This study sought to characterize the acute and short-term toxicities and tumor colonization rates of a genetically modified Salmonella typhimurium (VNP20009) in dogs with spontaneous tumors, in the context of a phase I dose escalation trial. Experimental Design: Forty-one pet dogs with a variety of malignant tumors received weekly or biweekly i.v. infusions of VNP20009, at doses ranging from 1.5 × 105 to 1 × 108 cfu/kg. Vital signs and clinicopathologic variables were monitored regularly. Incisional biopsies were obtained before and 1 week following the first infusion for histopathology and bacterial culture. Results: The nominal maximum tolerated dose was 3 × 107 cfu/kg, with refractory fever and vomiting being the dose-limiting toxicities. One treatment-related acute death occurred. Bacteria were cultured from tumor tissue in 42% of cases. Thirty-five patients were evaluable for antitumor response. Major antitumor responses were seen in 15% (4 complete response and 2 partial response), and disease stabilization for at least 6 weeks in 10%. Conclusions: Administration of VNP20009 at doses with acceptable toxicity results in detectable bacterial colonization of tumor tissue and significant antitumor activity in tumor-bearing dogs. |
| Databáze: | OpenAIRE |
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