Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist

Inclusion Criteria:

1. HLA-A\*0201 positive (to enable immunization with the HLA class I restricted gp100(g209-2M) peptide). Stage IIB or IIC patients will be enrolled after review and approval by the PI. (a tool to determine the projected survival at 5 years, like, but not limited to, the nomogram at www.melanomaprognosis.org. If the projected survival is less than 50% at 5 years, then the patient is considered for enrollment. This is with the recognition that the adjuvant, if effective offers a significant impact in that group of stage II patients.)
2. Patients \>/= 18 years old with histologically documented metastatic melanoma with a. (Metastatic disease cohort) Measurable disease, stage IIIB, IIIC (in transit lesions with or without nodal metastases) that includes lesions accessible for biopsies or IV M1B b. (Adjuvant cohort) subjects who are NED and stage III or IV. This includes patients with stage IV disease resected to NED. Stage IIB or IIC patients will be enrolled after review and approval by the PI.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
4. At least 2 biopsiable easily accessible cutaneous and subcutaneous lesions in patients in the metastatic disease cohort
5. White Blood Count (WBC) \>/= 3000/mm\^3 (part 1 \& 2)
6. Platelet count \>/= 90,000/mm\^3 (part 1 \& 2)
7. Serum alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) \</= 3 X upper limit of normal (ULN) (part 1 \& 2)
8. Total bilirubin \</= 2 X ULN, except for patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl Total bilirubin \</= 2 X ULN, except for patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (part 1 \& 2)
9. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)
10. Negative pregnancy test for women of childbearing potential (WOCBP) A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses at any time in the preceding 12 consecutive months)
11. Patients of both gender must practice a barrier method of birth control while participating in this trial.

Exclusion Criteria:

1. Active autoimmune disease requiring active therapy with any form of steroid or immunosuppressive therapy or a documented history of any of the following: inflammatory bowel disease; regional enteritis; systemic lupus erythematosis; Sjogren's syndrome; inflammatory neurologic disorder such as multiple sclerosis; or any immune mediated disease that can cause life-threatening symptoms or severe organ/tissue damage in the opinion of the principle investigator.
2. Concurrent systemic or inhaled steroid therapy
3. Any form of active primary or secondary immunodeficiency
4. Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years
5. History of immunization with gp100(g209-2M)
6. Active systemic infections requiring intravenous antibiotics
7. Women who are breastfeeding
8. Prior systemic therapy, radiation therapy or intracavitary surgery (intra-thoracic, intra-abdominal or intracranial) within 28 days of starting study treatment.
9. Patients on chronic anticoagulation such as Aspirin, Plavix, or Coumadin who cannot have anticoagulation held for procedures are not eligible due to the need for leukapheresis