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

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

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CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands.
Mol Ther Methods Clin Dev. 2020 Sep 11;18:839-855
Authors: Lombaert IMA, Patel VN, Jones CE, Villier DC, Canada AE, Moore MR, Berenstein E, Zheng C, Goldsmith CM, Chorini JA, Martin D, Zourelias L, Trombetta MG, Edwards PC, Meyer K, Ando D, Passineau MJ, Hoffman MP
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.

PMID: 32953934 [PubMed]