Preclinical pharmacology and toxicology of intravenous MV-NIS, an oncolytic measles virus administered with or without cyclophosphamide

R. M. Myers, S. M. Greiner, M. E. Harvey, G. Griesmann, M. J. Kuffel, S. A. Buhrow, J. M. Reid, M. Federspiel, M. M. Ames, D. Dingli, K. Schweikart, A. Welch, A. Dispenzieri, K. W. Peng, S. J. Russell

Research output: Contribution to journalArticle

88 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)700-710
Number of pages11
JournalClinical pharmacology and therapeutics
Volume82
Issue number6
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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