Inclusion Criteria:

• Histologically-confirmed, advanced/metastatic solid tumor refractory to standard therapy or the patient has refused or does not tolerate the standard therapy; tumors may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the head and neck
• At least one measurable tumor mass by CT/MRI (i.e. lesion that can accurately be measured in at least one dimension with longest diameter > 1 cm)
• At least one tumor mass amenable to biopsy and/or FNA
• Expected survival for approximately 16 weeks or longer
• Karnofsky Performance Score (KPS) ≥ 70
• Age ≥18 years
• WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3
• ANC ≥ 1,500 cells/mm3
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100,000 plts/mm3
• Total bilirubin ≤ 1.5 x ULN
• AST, ALT ≤ 2.5 x ULN
• Serum chemistries within normal limits (WNL) or Grade 1 - If patients are diabetic or have a screening random glucose > 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study.
• Acceptable coagulation status: INR ≤ (ULN + 10%)
• CD4 count ≥ 500/mm3

Exclusion Criteria:

• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
• Known myeloproliferative disorders requiring systemic therapy
• History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy
• Tumor(s) invading a major vascular structure (e.g. carotid artery)
• Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the upper airway or affecting biliary tract drainage, etc.)
• Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
• Severe or unstable cardiac disease
• Current, known CNS malignancy (history of completely resected or irradiated brain metastases allowed)
• Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
• Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.]
• Pulse oximetry O2 saturation <90% at rest
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination

Household contact exclusions:

• Women who are pregnant or nursing an infant
• Children < 5 years old
• History of exfoliative skin condition (e.g. eczema) that at some stage has required systemic therapy
• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)