The purpose of this study is to investigate a method of using dendritic cells (a kind of white blood cell) as a vaccine to stimulate your own immune system to react to your melanoma cells.

This is a single arm open label trial that will assess the safety and tolerability of mature dendritic cell (mDC3/8) vaccine (primer and booster) in subjects with stage III and stage IV melanoma, followed by treatment with pembrolizumab (anti-PD-1 therapy).

Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production approximately 1 week prior to vaccine infusion. Each study subject will receive cyclophosphamide 300mg/m^2 intravenously or by mouth 3 to 4 days prior to the vaccine dose, to deplete regulatory T cells. For each vaccine dose, all subjects will receive autologous dendritic cells pulsed with melanoma tumor-specific peptides. On Day 1, the subject will receive the primer vaccine dose; this will be followed by two booster vaccine doses at 6 weeks apart. Peripheral blood will be taken weekly to monitor the immune response to each peptide by tetramer assay. Re-staging will occur after the 3rd vaccine dose, along with tumor biopsy and second apheresis. Anti PD-1 therapy (standard of care) will commence 7-8 weeks after the subject's last dendritic cell vaccine.

Inclusion Criteria:

• Histologically confirmed stage III and stage IV M1a/M1b/M1c melanoma. Measurable disease is not required for enrollment eligibility and patients with completely resected disease are permitted.

• Male or female patients age greater than or equal to 18 years

• ECOG (Eastern Cooperative Oncology Group) performance status 0-2

• Required initial laboratory values (performed within 14 days prior to eligibility confirmation by physician-investigator):

  • WBC (white blood cells) >3,000/mm3
  • Hg (hemoglobin) greater than or equal to 9.0 gm/dl
  • Platelets >75,000/mm3
  • Serum Bilirubin < 2.0 mg/dl
  • Serum Creatinine < 2.0 mg/dl

• Subjects of reproductive potential must agree to use a medically accepted birth control method during the trial and for at least two months following the trial.

• Provide written informed consent.

Exclusion Criteria:

• Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment with one line of cytotoxic chemotherapy is permitted. Prior treatment with targeted therapy (such as ipilimumab, anti-PD1, or BRAF + MEK inhibitor combination) is permitted.
• Active untreated CNS (central nervous system) metastasis
• Active infection
• Prior malignancy (except non-melanoma skin cancer) within 3 years
• Pregnant or nursing (lactating) women
• Concurrent treatment with high-dose systemic corticosteroids; local (inhaled or topical) steroids are permitted
• Known allergy to eggs
• Prior history of uveitis or autoimmune inflammatory eye disease
• Known positivity for hepatitis B antibody, hepatitis C antibody, or HIV antibody

Collection of AEs will begin at the time of the first apheresis procedure (Apheresis #1) and continue until subject discontinuation or the End of Study Visit. (week 30).