Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease.

Inclusion Criteria:

* 18 years or older
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix A)
* Metastatic melanoma eligible for {or currently on} standard of care CPI therapy (treating physician's choice) with measurable disease.
* Approximately 1 cm3 preferred but 1 mg minimum of accessible and dispensable tumor (minimum of 3 passes with a core needle)
* Able to tolerate CPI treatment regimen {if already started}
* Adequate organ function as determined by the following laboratory values:
* ANC ≥ 1,000/μL
* Platelets ≥ 75,000/μL
* Hgb ≥ 9 g/dL
* Creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance ≥ 50% of lower limit of normal (LLN)
* Total bilirubin ≤ 1.5 ULN
* ALT and AST ≤ 1.5 ULN
* For women of child-bearing potential, agreement to use adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)

Exclusion Criteria:

* Inability to tolerate CPI therapy {if already started}
* Rapidly progressing multi-focal metastatic melanoma
* Insufficient tumor available to produce vaccine
* ECOG \>2 performance status (Appendix A)
* Immune deficiency disease or known history of HIV, HBV, HCV
* Receiving immunosuppressive therapy including chronic steroids (except physiologic maintenance doses), methotrexate, or other known immunosuppressive agents
* Pregnancy (assessed by urine HCG)
* Breast feeding
* Active pulmonary disease requiring medication to include multiple inhalers (\>2 inhalers and one containing steroids)
* Involved in other experimental protocols (except with permission of the other study PI)