Intratumoral Injection of Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Talimogene Laherparepvec (T-VEC)

Inclusion Criteria:

* Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
* Male or female age ≥ 18 years at the time of informed consent
* All subjects must have histologically confirmed advanced melanoma that cannot be completely surgically resected and have failed all standard curative and live prolonging therapy.
* All subjects must have non-visceral metastatic disease localizations that are amenable to intra-tumor injection by clinical and ultrasound (US) guidance. These metastases should be amenable to a safe post-injection biopsy (partial or complete).
* ECOG performance status of 0 or 1
* Candidate for intralesional therapy defined as either one of the following: a) at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion ≥ 10 mm in longest diameter, b) multiple injectable melanoma lesions that in aggregate have a longest diameter of ≥ 10 mm injectable disease
* Adequate organ function determined within 28 days prior to enrollment, defined as follows: a) Hematological, i) Absolute neutrophil count ≥ 1500/mm3 (1.5x109/L) ii) Platelet count: ≥ 75.000/mm3 (7.5x109/L) iii) Hemoglobin: ≥ 8 g/dL (without need for hematopoietic growth factor or transfusion support) b) Renal, i) Serum creatinine: 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN. (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard). c) Hepatic, i) Serum bilirubin: 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 1.5 x ULN ii) Aspartate aminotransferase (AST): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases iii) Alanine aminotransferase (ALT): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases d) Coagulation, i) International normalization ratio (INR) or prothrombin time (PT): 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants ii) PTT or aPTT: 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of intended use of
* Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Subject has a tumor sample (archival sample obtained within 3 months prior to study participation or newly obtained biopsy). Subject must submit the tumor sample during screening. Subjects with a non-evaluable archival sample may obtain a new biopsy and subjects with a non-evaluable newly obtained biopsy may undergo re-biopsy at the discretion of the investigator.
* Adequate vascular access to undergo a leucapheresis.

Exclusion Criteria:

* Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \>10 mg/day of prednisone or equivalent. The exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability.
* History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* History or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia)
* History of other malignancy within the past 5 years with the following exceptions: i) Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for \> 5 years before enrollment and felt to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment iii) Adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment iv) Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment v) Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment vi) Adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment
* Prior therapy with T-VEC or any other oncolytic viruses
* Prior treatment of other tumor vaccine
* Receive live vaccine within 28 days prior to enrollment
* Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
* Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
* Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management
* Other investigational procedures while participating in this study are excluded.