Development of Human‐Derived Cell Culture Lines for Recurrent Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) is mainly caused by human papillomavirus (HPV) 6 and 11. While various adjuvant therapies have been reported, no effective therapy has been documented to universally "cure" this disease. In the era of precision medicine, it would be valuable to identify effective intervention based on drug sensitivity testing and/or molecular analysis. It is essential to be able to successfully carry out in vitro culture and expand tumor cells directly from patients to accomplish this goal. Here we report the result of successful culture of HPV-infected cell lines (success rate 70%, 9/13) that express the E6/E7 RNA transcript, using pathologic tissue biopsies from patients treated at our institution. The availability of such a system would enable ex vivo therapeutic testing and disease modeling.

The crossroads: divergent roles of virus‐specific CD4+ T lymphocytes in determining the outcome for human papillomavirus infection

“…Using MHC class II tetramers refolded with immunogenic HPV11 E2 (01-20), E2 (281-300) and E6 (113-132) peptides, antigen-specific CD4 + T lymphocytes were isolated, cultured and found to be deficient in STAT5 (signal transducer and activator of transcription 5) phosphorylation and production of IL-2, suggesting an anergic state. It is for this reason that HPV vaccination is commonly employed, perhaps in concert with adjuvant 82,83 or checkpoint inhibitor immunotherapy (e.g. pembrolizumab) 84,85 as a form of treatment for RRP to boost humoral and CD4 + T-lymphocyte immunity.…”

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

“…Advances in medical treatments for RRP have been reported recently 8–10 . However, delays in RRP treatment development have been frequently attributed to a lack of preclinical models 9,11–13 . Preclinical models of HPV‐positive laryngeal SCC have not been widely reported because laryngeal SCC is associated primarily with smoking rather than HPV infection 14–16 .…”

How Enhancing Immunity to Low‐Risk HPV Could Cure Recurrent Respiratory Papillomatosis

“…Numerous adjuvant treatments have been used to treat RRP, including antivirals and antiangiogenics. The difficult nature of establishing in vitro or in vivo models of chronic low‐risk HPV infection that causes papillomatous disease has made preclinical research slow and challenging 7,8 . As a result, most published research in RRP is clinical research.…”

“…The difficult nature of establishing in vitro or in vivo models of chronic low-risk HPV infection that causes papillomatous disease has made preclinical research slow and challenging. 7,8 As a result, most published research in RRP is clinical research. Because large prospective clinical trials studying new RRP treatment are difficult to fund and accrue, most published clinical research studies are the result of small retrospective, uncontrolled, single-cohort studies using Food and Drug Administration (FDA)-approved drugs with other indications.…”