Haploidentical NK Cell Infusion in Malignant Melanoma

Human NK cells recognize and kill transformed cells in a MHC-unrestricted fashion, suggesting the role of cancer immunotherapy. However, autologous NK cells showed the lack of significant clinical effects, because they are inhibited by self MHC class I molecules, based on the missing-self hypothesis. Contrarily, haploidentical NK cells with KIR-ligand incompatibility can mediate graft-versus-leukemia effect and protect patients with acute myelogenous leukemia (AML) from graft-versus-host disease. In addition, adoptive transfer of haploidentical NK cells following high-intensity conditioning induced complete remission (26%) in poor-prognosis AML patients. Thus, this study was designed to investigate the role of adoptive NK cell therapy in patients with refractory or relapsed malignant melanoma using CD3+ depleting CliniMACS® system.

Inclusion criteria

• Histologically confirmed metastatic or relapsed malignant melanoma
• Patients who received prior chemotherapy or immunotherapy
• Patients who have at least one haploidentical donor willing to donate
• ECOG performance status 0 or 1
• 18 - 75 years
• At least one measurable disease according to the RECIST criteria
• Patients with 45% or more left ventricular ejection fraction
• Patients with 50% or more predicted DLCO
• Adequate bone marrow function: absolute neutrophil count ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; and hemoglobin ≥ 9 g/dL
• Adequate liver function: total bilirubin ≤ 1.0 x upper limit of the normal range (ULN); AST/ALT ≤ 2.5 x ULN; and alkaline phosphatase ≤ 2.5 x ULN
• Adequate renal function: serum creatinine ≤ 1.0 x ULN or creatinine clearance ≥ 60 mL/min/1.73m2
• At least 3 months of expected survival
• Patients who signed informed consent

Exclusion criteria

• Patients who received other chemotherapeutic agents within 30 days prior to study enrollment
• Patients who received adoptive cell therapy including hematopoietic stem cell transplantation
• Patients infected with HIV, HBV, or HCV
• Hypersensitivity to cyclophosphamide or interleukin-2
• Patients who received organ transplantation
• Patients who had arrhythmia or ischemic heart disease
• Pregnant or lactating women
• Patients with uncontrolled infection who did not respond to appropriate antimicrobial agents