Xenograft Model for Therapeutic Drug Testing in Recurrent Respiratory Papillomatosis

Julie Ahn, Justin A. Bishop, Belinda Akpeng, Sara I. Pai, Simon R.A. Best

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. Methods: A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgammanull (NSG) mouse. Results: The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. Conclusion: We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.

Original languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalAnnals of Otology, Rhinology and Laryngology
Volume124
Issue number2
DOIs
StatePublished - Feb 1 2015

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Keywords

  • bevacizumab
  • drug testing
  • laryngeal papilloma
  • larynx
  • papilloma
  • pulmonary papilloma
  • recurrent respiratory papillomatosis
  • xenograft

ASJC Scopus subject areas

  • Otorhinolaryngology

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