Inclusion Criteria:

• Patients must have given signed informed consent for participation in the study prior to any study-related procedures being performed and not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Age ≥18 years of age and ≤75 years of age
• Histologically confirmed, unresectable stage 3 or 4 measurable (RECIST criteria), cutaneous melanoma or unknown primary with melanoma metastases
• Life expectancy of at least 30 weeks and an ECOG performance status of X 1
• Adequate renal and liver function as defined by serum creatinine and total bilirubin levels no greater than 1.5 times the Investigational Site's upper normal laboratory limits
• Normal clotting
• The patient is willing and able to comply with the protocol for the duration of the study, including 2 hours of follow up observation after the injections (until DMC lifts it after analysis of the first 20 injections) during the course of the trial, examinations and punch biopsies of the vaccination sites 48 hrs post vaccine 1 (week 0) and 8 (week14).

Exclusion Criteria:

• Any previous participation in another trial with the AGI - 101 vaccine
• Ocular or mucosal melanoma
• Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used (lack of childbearing potential is met by being post-menopausal, being surgically sterile, practicing contraception with an oral contraceptive or other hormonal therapy [e.g. hormone implants], intra-uterine device, diaphragm with spermicide or condom with spermicide, or being sexually inactive)
• Radiotherapy to target lesions or immunotherapy (including treatment with Interferon or Interleukin-2 and systemic glucocorticosteroids) during the four weeks prior to the start of study treatment.
• Any previous treatment with systemic chemotherapy for advanced melanoma
• Brain metastases
• Major surgery in the four weeks prior to the start of study treatment
• Patients who are poor medical risks due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
• Patients who are known to be serologically positive for Hepatitis B (patients vaccinated against Hepatitis B are accepted), Hepatitis C or HIV
• States causing significant immunosuppression (e.g. organ transplantation or haemodialysis).
• Simultaneous participation in any other study involving investigational drugs or having participated in a study less than 4 weeks prior to start of study treatment.