Journal Article

DKFZ-2023-00490

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice.

Schifflers, C. (First author)DKFZ* ; Zottnick, S.DKFZ* ; Förster, J.DKFZ* ; Kruse, S.DKFZ* ; Yang, R.DKFZ* ; Wiethoff, H.DKFZ* ; Bozza, M.DKFZ* ; Hoppe-Seyler, K.DKFZ* ; Heikenwälder, M.DKFZ* ; Harbottle, R. P.DKFZ* ; Michiels, C. ; Riemer, A. (Last author)DKFZ*

2023
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/pathogens12020188

Abstract: Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities.

Keyword(s): head and neck squamous cell carcinoma ; human papillomavirus ; orthotopic tumor model

Note: #EA:F130#LA:F130#

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Contributing Institute(s):

1. F130 Immuntherapie und -prävention (F130)
2. F030 Virale Transformationsmechanismen (F030)
3. F190 NWG Cell Plasticity and Epigenetic Remodeling (F190)
4. F160 DNA-Vektoren (F160)
5. F065 Molek. Therapie virusassozierter Tumore (F065)
6. F180 Chronische Entzündung und Krebs (F180)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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Database coverage:
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