Inclusion Criteria:

- Diagnosis of histologically or cytologically documented, malignant pleural effusions
(primary non-small-cell lung carcinoma, mesothelioma, and other histologies), who
have free pleural space (partial or total) that permits the intrapleural drug
instillation. This includes cytologically negative pleural effusion in conjunction
with histologically proven malignancy involving the pleura.

- Age must be ≥ 18 years.

- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical
procedures must have resolved to Common Terminology Criteria for Adverse Events
(CTCAE, Version 4.0) Grade ≤ 1. Any surgery, where anesthesia was administered, must
have occurred at least 14 days prior to study enrollment.

- Chemotherapy, radiotherapy or immunotherapy must have stopped more than 14 days prior
to receiving study drug; however, small field palliative radiotherapy, TKI therapies
and hormonal therapies are allowed.

- Patients with stage IV NSCLC must have had a brain scan (MRI or CT with contrast)
showing no evidence of disease progression within 8 weeks of study enrollment.

- ECOG Zubrod ≤ 2.

- Required baseline laboratory data include:

Absolute neutrophil count (ANC) ≥ 1.5 × 109 [SI units 10^9/L],

- Platelets ≥ 100 ×10^9 [SI units 10^9/L],

- Hemoglobin ≥ 9.0 g/dL [SI units gm/L],

- Serum creatinine ≤ 1.5 × upper limit of normal (ULN),

- Bilirubin ≤ 1.5 × ULN,

- AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases)

- Negative pregnancy test for females of childbearing potential.

Exclusion Criteria:

- Pregnant or breast-feeding women.

- Patients with fever or any active systemic infections, including known HIV, hepatitis
B or C.

- Patients on immunosuppressive therapy or with immune system disorders, including
autoimmune diseases.

- Concurrent steroid use of more than an equivalent of 20 mg/day prednisone (or
equivalent).

- Prior splenectomy.

- Previous organ transplant.

- Patients with clinically significant dermatological disorders, e.g., eczema or
psoriasis, as judged by the principal investigator, or any unhealed skin wounds or
ulcers.

- Clinically significant cardiac disease (New York Heart Association, Class III or IV).

- Dementia or altered mental status that would prohibit informed consent.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality, that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results and,
in the judgment of the principal investigator, would make the patient inappropriate
for this study.

- Known allergy to ovalbumin or other egg products.

- Prior gene therapy treatments or prior therapy with cytolytic virus of any type.

- Concurrent therapy with any other investigational anticancer agent.

- Concurrent antiviral agent active against vaccinia virus (e.g. cidofovir, vaccinia
immunoglobulin) during the study.