CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands

Abstract

Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Lombaert, I. M. A., Patel, V. N., Jones, C. E., Villier, D. C., Canada, A. E., Moore, M. R., Berenstein, E., Zheng, C., Goldsmith, C. M., Chorini, J. A., Martin, D., Zourelias, L., Trombetta, M. G., Edwards, P. C., Meyer, K., Ando, D., Passineau, M. J., & Hoffman, M. P. (2020). CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands. Molecular Therapy - Methods & Clinical Development, 18, 839–855. https://doi.org/10.1016/j.omtm.2020.07.016
ISSN
2329-0501
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Molecular Therapy - Methods & Clinical Development
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Full Text Available at
This item is under embargo {{howLong}}