Preclinical pharmacology and toxicology of intravenous MV-NIS, an oncolytic measles virus administered with or without cyclophosphamide.
Clin Pharmacol Ther
; 82(6): 700-10, 2007 Dec.
Article
en En
| MEDLINE
| ID: mdl-17971816
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 x 10(6) 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 10(8) and 4 x 10(8) 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 x 10(4) TCID50/kg (10(6) TCID50 per patient).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ciclofosfamida
/
Simportadores
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Virus Oncolíticos
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Viroterapia Oncolítica
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Virus del Sarampión
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Mieloma Múltiple
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Antineoplásicos
Tipo de estudio:
Guideline
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos