Engineered oncolytic virus for the treatment of cholesteatoma: A pilot in vivo study

Abstract

Objective Determine if oncolytic herpes simplex virus (oHSV) can eradicate cholesteatoma (CHST) in a gerbil model. Methods An in vivo model of CHST was developed in Mongolian gerbils by combining Pseudomonas aeruginosa inoculation with double ligation of the external auditory canal (EAC). CHST size and bone thickness were measured using morphometric and volumetric quantification techniques via micro‐computed tomography (micro‐CT). The CHST induction and quantification techniques were then used in an additional group of 10 gerbils (n = 20 ears) to determine the within‐group treatment efficacy of oHSV against CHST in vivo. Treated animals received either one, two, or three intrabullar injections of oHSV between 2 and 6 weeks postinduction of CHST. Results The P. aeruginosa inoculation plus double EAC ligation technique successfully induced a range of CHST growth in 100% of the ears in the model‐development group. Osteolytic effects of CHST were observed in 6% of ears whereas osteoblastic effects were observed in 31% of ears. CHST volume decreased by 50% or more in 12 of the 20 ears in the oHSV‐treatment groups. An apparent reversal of osteoblastic effects was also observed in three out of four ears 6 weeks following the third oHSV injection. Conclusions P. aeruginosa inoculation plus double EAC ligation reliably induces CHST formation in gerbil. CT‐based volumetric measures are significantly more accurate than single‐slice morphometric area measures for quantification of CHST size. Treatment with oHSV appears to be efficacious for reducing CHST volume by as much as 77% with as few as one treatment. Level of Evidence NA

Keywords

• Cholesteatoma
• oncolytic virotherapy
• oHSV