INCLUSION CRITERIA:
-Age 18 years of age or older.
-Capable of providing informed consent.
-History of radiation therapy for head and neck cancer, having received greater than 45Gy to the parotid gland(s) due to primary or neck radiation.
-Abnormal parotid gland function in the targeted parotid gland as judged by absence of unstimulated parotid salivary flow and a stimulated parotid salivary flow in the targeted parotid gland less than 0.2 mL/min/gland after 2 percent citrate stimulation.
-Abnormal (99m)TcO4 scintiscan (reduced or absent uptake of (99m)TcO4) for the targeted parotid gland in the following circumstance: A (99m)TcO4 scintiscan will only be performed and used to determine eligibility if the isotope is available. If the isotope is not available, this inclusion criterion is not applicable.
-Abnormal sialograms (an altered ductal network with sialectasis) for the targeted parotid gland.
-No current evidence of malignancy by otolaryngology assessment, including a clinical history, nasopharyngolaryngoscopy, and negative CT or PET scan.
-Must be disease-free for at least 5 years, with the disease-free interval calculated from date of last cancer treatment (i.e. date of last radiation, chemotherapy or surgery) to date of pre-dose screening.
-Willingness to practice appropriate birth control methods (preferably "barrier" contraception, i.e., condoms, diaphragm) until AdhAQP1 is no longer detectable in their serum or saliva. Women who cannot bear children (post menopausal or due to a surgical intervention) will be asked to practice barrier birth control methods until AdhAQP1 is no longer detectable in their serum or saliva.
-Able to stay at the NIH hospital for the period of time necessary to complete each on-site phase of the protocol.
-No history of allergies to any medications or agents to be used in this protocol.
-On stable doses of medications (greater than or equal to 2 months from the pre-dose screening visit) for any underlying medical conditions.
EXCLUSION CRITERIA:
-Pregnant or lactating women. Women of childbearing potential are required to have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours of treatment.
-Any experimental therapy within 3 month of planned AdhAQP1 administration (Day 1).
-Any active respiratory tract infection in the 3 weeks prior to planned AdhAQP1 administration (Day 1).
-Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before planned AdhAQP1 administration (Day 1).
-Evidence of active substance or alcohol abuse or history of substance or alcohol abuse within two years of screening.
-Uncontrolled ischemic heart disease: unstable angina, evidence of active ischemic heart disease on ECG, congestive heart failure (left ventricular ejection fraction less than 45 percent on MUGA or echo) or cardiomyopathy.
-Asthma or chronic obstructive pulmonary disease requiring regular inhaled or systemic corticosteroids.
-Individuals taking prescription medications (anti-cholinergics, anti-depressants) likely to result in salivary hypofunction.
-Individuals with a history of autoimmune diseases affecting salivary glands, including Sjogren's syndrome, lupus, scleroderma, type 1 diabetes, sarcoidosis, amyloidosis, and chronic graft versus host disease.
-Use of systemic immunosuppressive medications, e.g., corticosteroids. Topical corticosteroids are allowed.
-History of a second malignancy, within past 3 years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
-Active hepatitis B, hepatitis C or HIV infection.
-WBC less than 3000/microL or ANC less than 1500/microL or Hgb less than 10.0 g/dL or platelets less than 100,000/microL or absolute lymphocyte count less than or equal to 500//microL.
-ALT and/or AST greater than 1.5x upper limit of normal (ULN) or alkaline phosphatase greater than 1.5x ULN.
-Serum creatinine greater than 2 mg/dL.
-Individuals who are active smokers.
-Individuals who consume more than 1 alcoholic beverage/day
-Individuals who have an allergy to iodine or shellfish and thus are unable to have sialographic evaluations.
-Individuals whose parotid ducts is not clinically accessible on screening sialography evaluations.
-Individuals who on sialography have a distal stenosis in the taregeted parotid gland that would impede vector delivery.
-Individuals who likely would require use of a general anesthetic for ultrasound-guided core needle biopsy (applicable only for participants in dose cohorts 2-5).
-Significant concurrent or recently diagnosed (less than 2 months from Day 1) medical condition that, in the opinion of the Medically Responsible Investigator, could affect the participant's ability to tolerate or complete the study.
-Live vaccines within 4 weeks of first infusion.
-Previous participation in a rAd5 vector gene transfer study.