This clinical trial is to determine if the addition of a standard of care drug, interferon-alfa 2b (IFN), with an investigation vaccine will have any affect on the immune system and/or your cancer. The investigational vaccine will be made with genes that are specific to melanoma and will be given intradermally (i.d.) every two weeks for a total of 3 vaccines.

After the vaccines, subjects will be randomized to either receive a boost of high dose IFN or no boost. IFN will be administered intravenously (into a vein) for 5 consecutive days (Monday through Friday) every week for 4 weeks. Administration will begin approximately 30 days (± 7 days) after the 3rd vaccine. The first dose of IFNα2b may begin within 10 business days of randomization. All subsequent procedure dates for Group A will be based on the date of the first dose of IFNα2b.

This is a Phase I, single site study to evaluate the immunological effects of autologous DC transduced with the MART-1, tyrosinase and MAGE-A6 (melanoma associated antigens, MAA) genes in 30 subjects with recurrent, unresectable stage III, IV metastatic melanoma (M1a, M1b, M1c). AdVTMM2-transduced DC, 10e7, will be given intradermally (i.d.) every two weeks for a total of 3 vaccines.

After the DC vaccines, subjects will be randomized to either receive a boost of high dose IFNa2b or no boost.

Subjects randomized to receive the IFNa2b boost will receive Interferon-a2b, 20 MU/m2/d (rounded to the nearest 1 million units) administered intravenously for 5 consecutive days (Monday through Friday) every week for 4 weeks (induction). Administration will begin approximately 30 days (± 7 days) after the 3rd vaccine. The first dose of IFNα2b may begin within 10 business days of randomization. All subsequent procedure dates for Group A will be based on the date of the first dose of IFNα2b..

The end-points of this study are local and systemic toxicity, immunological response, generation of determinant spreading and anti-tumor immunity, and clinical response.

Inclusion Criteria:

• Ability and willing to give consent
• Patients age 18 and older with recurrent, inoperable stage III, IV, M1a, b or c melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC).

Previously treated with any form of therapy (including chemotherapy, radiation therapy, immunotherapy or surgery) for either metastatic, relapsed, or primary melanoma are eligible for this trial, provided the previous treatment was completed > 30 days prior to enrollment.

• Patients should have at least 2 subcutaneous, intracutaneous, and accessible tumor deposits, lymph node or other site available for biopsy purposes.
• Both men and women may be enrolled. Premenopausal females must have a negative pregnancy test prior to treatment and lactating females will have to discontinue breast feeding to be eligible.
• ECOG Performance Status of 0 or 1.
• No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease.
• No previous evidence of opportunistic infection.
• Adequate baseline hematological and organ function as assessed by the following laboratory values within 28 days prior to study entry:

Hemoglobin >/=9 g/dL Granulocytes >/=2,000/mm3 Lymphocytes >/=1000/mm3 Platelets >100,000/mm3 Serum Creatinine \