IMCgp100 in Advanced Unresectable Melanoma

Inclusion Criteria:

* 1\. Histologically confirmed diagnosis of melanoma, with advanced unresectable disease not currently requiring immediate treatment and/or in a window between treatments.
* 2\. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7-15 mm in at least one dimension and amenable to subsequent biopsy.
* 3\. Age 18 years
* 4\. ECOG performance status 0-2
* 5\. Able to understand and to provide written informed consent and willingness to comply with all protocol requirements;
* 6\. Female patients who are not be of childbearing potential as documented by medical history (e.g., tubal ligation or hysterectomy), or be post menopausal with a minimum 1 year without menses or have a negative serum beta human chorionic gonadotropin (HGC) pregnancy test within 48 hours prior to receiving the intratumoral injection and agree to use an acceptable form of birth control, defined as abstinence or use of an intrauterine device (IUD), oral contraceptive, barrier and spermicide, or hormonal implant throughout the study period;
* 7\. Male patients who must agree to use an acceptable form of birth control throughout the study period.
* 8\. Adequate organ system function as evidenced by laboratory values: -Absolute neutrophil count (ANC) greater than or equal to 1.0 X 109/L -Hemoglobin greater than or equal to 9 g/dL -Platelets greater than or equal to 75 X 109/L -Total bilirubin less than or equal to 1.5 mg/dL -AST and ALT less than or equal to 2.5 X ULN ( 2.5 X ULN in the presence of liver metastasis.) -Creatinine less than or equal to 2 mg/dL -TSH within normal limits -INR/PT and PTT less than or equal to 1.3 X ULN

Exclusion Criteria:

* 1\. Receive any chemotherapy, immunotherapy, radiation therapy, or other investigational agents (agents part of a research protocol or not approved by the FDA) within 2 weeks prior to injection. A minimum of 14 days is required between last therapy and injection on this study. In addition, any clinically significant drug-related toxicity should have recovered to grade 1 or less (excluding alopecia)
* 2\. Patients without cutaneous or subcutaneous metastatic lesions;
* 3\. Cutaneous metastases that have received prior local therapy, such as radiation or isolated limb perfusion.
* 4\. Pregnancy or breastfeeding
* 5\. History of autoimmune disease (excluding vitiligo or controlled thyroid disease) or immunodeficiency.
* 6\. Current treatment with steroids (inhaled, topical or systemic) or other immunosuppressive medications within 2 weeks of injection;
* 7\. Active uncontrolled infection;
* 8\. Known HIV positivity;
* 9\. Uncontrollable seizures;
* 10\. Known delayed wound healing;
* 11\. Full dose anticoagulation with heparin, warfarin, or any other anticoagulant within 2 weeks of injection ;
* 12\. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting, stroke or TIA within the past 24 weeks.;
* 13\. Known hypersensitivity of IMCgp100 or any of its components (ie, Tween) ;
* 14\. Class II, III, or IV heart failure as defined by the New York Heart Association;
* 15\. Any psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
* 16\. Any other condition that in the investigators opinion would jeopardize compliance with the protocol ;