Inclusion Criteria:

• Greater than 18 years of age
• Histologically-confirmed injectable cancer mass (≤ 10 cm. maximum diameter ) that has progressed despite standard therapy; and is amenable to injection and biopsy. They must have one of the following tumor-types: melanoma, breast cancer, or head and neck squamous cell cancer, hepatocellular, colorectal or pancreatic
• Cancer is not surgically curable
• Karnofsky Performance Status (KPS) of > 70
• Anticipated survival of at least 16 weeks
• If sexually-active, willingness to use condoms for 3 months following treatment with vvDD-CDSR
• The ability to understand and willingness to sign a written informed consent
• Able to comply with study procedures and follow-up examinations
• Adequate bone marrow function: WBC > 3,500 and <50,000 cells/mm3 , ANC > 1,500 cells/mm3, hemoglobin > 10 g/dL, and platelet count > 150,000 cells/mm3
• Adequate renal function: serum creatinine < 1.2 mg/dL
• Adequate hepatic function: AST (≤ 1.5 ULN), ALT (≤ 1.5 ULN), total bilirubin (< 2.0 ULN)
• Acceptable coagulation status: INR<(ULN +10%)

Exclusion Criteria:

• Pregnant or nursing an infant
• Active viral infection (including HIV, Hepatitis B or C)
• Systemic corticosteroid or other immunosuppressive medication use within 4 weeks of the treatment
• Clinically significant active infection or uncontrolled medical condition (e.g., pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment
• Significant immunodeficiency (e.g. due to underlying illness and/ or medication) in subject or household contacts
• History of eczema requiring systemic therapy
• Unstable cardiac disease which includes but is not limited to: Any of the following within 6 months prior to study entry: MI, unstable angina, congestive heart failure, myocarditis, arrhythmias diagnosed and requiring medication, or any clinically-significant change in cardiac status
• Target tumor(s) adherent to a major vascular structure (e.g. carotid artery)
• Participation in any investigational drug study, radiotherapy, chemotherapy or surgery within 4 weeks of study entry; NOTE: For subjects who have received radiotherapy, chemotherapy, or other potentially immunosuppressive therapy a CD4 T cell count will be performed as part of the screening procedures. If the CD4 T cell count is < 350 per µl blood subjects will not be allowed to participate due to their immunosuppressed state
• Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
• Subjects with household contacts who are pregnant or nursing an infant, children < 5 years old, have history of eczema that at some stage has required systemic therapy, or have a significant immunodeficiency due to underlying illness (e.g. HIV) and/or medication (e.g. systemic corticosteroids) will be excluded unless alternate living arrangements can be made during the subject's active dosing period and for three weeks following the last dose of study medication
• Inability or unwillingness to give informed consent.