Premium
Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide
Author(s) -
Myers R M,
Greiner S M,
Harvey M E,
Griesmann G,
Kuffel M J,
Buhrow S A,
Reid J M,
Federspiel M,
Ames M M,
Dingli D,
Schweikart K,
Welch A,
Dispenzieri A,
Peng KW,
Russell S J
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100409
Subject(s) - oncolytic virus , cyclophosphamide , pharmacology , measles virus , medicine , clinical pharmacology , measles , toxicity , virology , virus , chemotherapy , vaccination
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 × 10 6 TCID 50 (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 10 8 and 4 × 10 8 TCID 50 /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 × 10 4 TCID 50 /kg (10 6 TCID 50 per patient). Clinical Pharmacology & Therapeutics (2007) 82 , 700–710; doi: 10.1038/sj.clpt.6100409 ; published online 31 October 2007