1. ¹Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
2. ²Toxicology Core, Mayo Clinic, Rochester, Minnesota, USA
3. ³Viral Vector Production Laboratory, Mayo Clinic, Rochester, Minnesota, USA
4. ⁴Department of Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA
5. ⁵Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
6. ⁶Toxicology and Pharmacology Branch, Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland, USA
7. ⁷Biological Resources Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, Maryland, USA

Correspondence: SJ Russell, (sjr@mayo.edu)

Received 21 August 2007; Accepted 6 September 2007; Published online 31 October 2007.

Abstract

MV-NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol "Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, with or without Cyclophosphamide, in Patients with Recurrent or Refractory Multiple Myeloma." Dose–response studies in the KAS-6/1 myeloma xenograft model demonstrated a minimum effective dose of 4 10⁶ TCID₅₀ (tissue culture infectious dose 50)/kg. Toxicity studies in measles-naive squirrel monkeys and measles-susceptible transgenic mice were negative at intravenous doses up to 10⁸ and 4 10⁸ TCID₅₀/kg, respectively. Abundant viral mRNA, maximal on day 8, was detected in cheek swabs of squirrel monkeys, more so after pretreatment with cyclophosphamide. On the basis of these data, the safe starting dose of MV-NIS for our clinical protocol was set at 1-2 10⁴ TCID₅₀/kg (10⁶ TCID₅₀ per patient).