Combination of CARTs, CTLs and DC Vaccines Targeting Melanoma
The purpose of this study is to assess the feasibility, safety and efficacy of combination immunotherapy based on CAR T cells, cytotoxic T lymphocytes (CTLs), and dendritic cell (DC) vaccines modified with GM-CSF and B7-2 (CD86) against melanoma, which targets CAR T specific surface antigens such as GD2, CTL specific antigens such as MAGE-A4, gp100 and a pool of melanoma specific antigens presented by the DCs. Another goal of the study is to learn more about the function and persistence of the CAR T cells and antigen-specific immune effectors in patients.
• Patients with melanoma have received standard first-line therapy and have been diagnosed with non-resectable, metastatic, progressive or recurrent conditions.
• The expression of melanoma specific antigens is immunohistochemically stained and verified.
• 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:
‣ There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must be resolved to grade 2 or less.
⁃ Participants must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
⁃ 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.
⁃ At least 4 weeks must have elapsed since prior therapy that includes a monoclonal antibody.
⁃ 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, the patients or their legal guardians must sign an informed consent and assent.