NG2 and DLL3 CAR-T Cells Targeting Melanoma

Inclusion Criteria:

* Patients with tumors have received standard first-line therapy and have been diagnosed with non-resectable, metastatic, progressive or recurrent conditions.
* The expression status of NG2 and DLL3 antigens of the tumor has been determined for eligibility. Positive expression is defined by NG2 and DLL3 antibody staining results based on immunohistochemistry or flow cytometry analyses.
* Body weight greater than or equal to 40 kg.
* Age: ≥18 year and ≤ 75 years of age at the time of enrollment.
* Life expectancy: at least 8 weeks.
* Prior Therapy:

  1. There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.
  2. Participants must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
  3. At least 7 days must have elapsed since the completion of therapy with any biologic agent, targeted agent, tyrosine kinase inhibitor or metronomic non-myelosuppressive regimen.
  4. At least 4 weeks must have elapsed since prior therapy that includes a monoclonal antibody.
  5. At least 1 week must has elapsed since any radiation therapy at the time of study entry.
* Karnofsky/jansky score of 70% or greater.
* Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
* Pulse Ox greater than or equal to 90% on room air.
* Liver function: defined as alanine transaminase (ALT) \<3x upper limit of normal (ULN), aspartate aminotransferase (AST) \<3x ULN; serum bilirubin and alkaline phosphatase \<2x ULN.
* Renal function: Patients must have serum creatinine less than 3 times ULN.
* Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
* Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable for hematologic toxicity.
* For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

* Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
* Untreated central nervous system (CNS) metastasis; patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
* Previous treatment with other genetically engineered CAR T cells.
* Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
* Patients who require systemic corticosteroid or other immunosuppressive therapy.
* Evidence of tumor potentially causing airway obstruction.
* Inability to comply with protocol requirements.
* Insufficient availability of CART cells.