This research will study how to activate the immune system by using gene transfer. Gene transfer involves inserting a specially designed gene into cancer cells. A gene is a part of the genetic code that instructs the cells of our bodies to produce specific compounds (proteins) important for the makeup or function of the cell. The study hypothesis is that repeated doses of SCH 721015 given over a three day interval would result in gene transfer.

Ad.hIFN-α (SCH 721015, adenoviral-mediated interferon alpha) is a replication-defective recombinant adenoviral vector containing the human interferon-alpha (hIFN-alpha) gene. This Phase I study is designed to evaluate the safety and maximum tolerated dose (MTD) of two doses of Ad.hIFN-alpha injected into the pleural (intrapleural, IP) and given 4 days apart in subjects with pleural mesothelioma.

Subjects who meet eligibility will have a pleural catheter placed 2 weeks prior to the first dose. Subjects are then admitted to the research center on Days 1 and 4 for dosing and overnight observation. Subjects are then followed-up as outpatients for a total of 6 months. Radiographic evaluations are repeated on Day 64 and at 6 months. The pleural catheter is removed once it is not necessary.

Inclusion Criteria:

• evidence of progressive disease after standard first line treatment of mesothelioma; OR patient has refused standard first line treatment of mesothelioma
• evaluable disease
• No radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 14 days prior to infusion of the IFN-α vector
• Must have a pleural space involved with tumor accessible for pleural catheter insertion
• FEV1> 1 liter or 40% of predicted value
• Must have an anti-adenoviral neutralizing antibody titer equal to or less than 1:1000. This will be measured by the Penn Vector Core

Exclusion Criteria:

• Presence of HIV or Hepatitis B infection
• Use of concurrent systemic steroids, immunosuppressives, or any other medications that can directly or indirectly suppress the immune system
• Presence of any other life-threatening illness, such as unstable angina, severe oxygen dependence, significant chronic obstructive pulmonary disease (COPD), end stage liver or renal disease
• Presence of untreated brain metastases
• Prior bone marrow or stem cell transplants