Combination Gene Transfer and Chemotherapy

Inclusion Criteria: * -Pathologically documented malignant mesothelioma * Must have evaluable disease by RECIST or Modified RECIST Criteria. * ECOG Performance status equal to or lesser than 1. * Must be at least 18 years of age. * Women of childbearing potential and men must use acceptable contraceptive methods during treatment. * Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. * Must be able and willing to give written informed consent. * No radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 4 weeks prior to infusion of the IFN-alpha vector. * Must have pleural tumor accessible for pleural catheter insertion. Patients with a previously inserted pleural catheter may enroll in the trial and can use the preexisting catheter for vector infusion as long as it is functional and has no evidence of local infection. * FEV1 equal to or lesser than 1 liter or 40% of predicted value (post-pleural drainage). * Acceptable hematologic value: granulocyte count equal to or lesser than 1,500/mm3, hemoglobin equal to or lesser than 9 g/dl, platelets equal to or lesser than 100,000/mm3 * Acceptable liver function: bilirubin equal to or less than 1.5 x the upper limit of normal; ALT, AST, and alkaline phosphatase equal to or less than 2.0 x the upper limit of normal * Acceptable kidney function: creatinine less than 2.0 mg/dl (less than 1.5 mg/dl required for Cisplatin administration) or Creatinine clearance greater than 50. * Acceptable coagulation status: PT equal to or less than 1.5 x normal, PTT less than 1.5 x normal. However, patients on stable, chronic anti-coagulation therapy with therapeutic anti-coagulation levels will be allowed to enroll in the study. * Serum albumin must be greater than 2.5 g/dl * Must have an anti-adenoviral neutralizing antibody titer equal to or less than 1:1000. This will be measured by sub-investigators in the Thoracic Oncology Research Laboratory under standardized (but not GCP) conditions. Results must be known before performing any other research procedures. * Must have medical insurance coverage (or other means of payment) providing for standard medical interventions in clinical trial, including combination chemotherapy. Exclusion Criteria: * Presence of significant pericardial effusion on baseline CT scan of the chest. * Documented immunodeficiency such as HIV infection. * Evidence of chronic active Hepatitis B (positive for HBsAg). Prior HBV exposure without evidence of chronic active Hepatitis B is not exclusionary. * Use of concurrent systemic steroids (greater than10 mg of prednisone per day), 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. * Rapidly re-accumulating,symptomatic malignant pleural effusion status-post thoracentesis or pleural catheter insertion that requires immediate mechanical or chemical pleurodesis for adequate palliation. * Presence of untreated brain metastases. Subjects with a prior history of brain metastases will have a CT or MRI scan of the brain to rule out activity. * Prior bone marrow or stem cell transplants -Female patients who are actively nursing are excluded. * Patients who have undergone any prior major surgery (excluding pleural catheter placement or infusaport insertion) less than 2 weeks prior to study enrollment. * Lack of medical insurance coverage (or other form of payment) for standard medical interventions, particularly combination chemotherapy.