Supplementary Figure S1. Clinical treatment protocol; Supplementary Figure S2. Characterization of ex vivo-expanded NK cells; Supplementary Figure S3. Analysis of donor KIR genotype and clinical outcome; Supplementary Figure S4. Kinetics of donor NK cells in the peripheral blood of recipients; Supplementary Figure S5. NKG2D expression on NK and T cells in patients' peripheral blood.
Funding
Green Cross Corporation,MOGAM Biotechnology Institute, and the Innovative Research Institute for Cell Therapy, Republic of Korea
ARTICLE ABSTRACT
Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor–ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo–expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors. The maximum dose (3 × 107 cells/kg, triple infusion) was tolerable without significant adverse events. Of 17 evaluable patients, 8 patients (47.1%) showed stable disease and 9 (52.9%) showed progressive disease. We also evaluated the capacity of MG4101 to influence host immune responses. Administration of MG4101 augmented NKG2D expression on CD8+ T cells and upregulated chemokines that recruit T cells. In contrast, administration of MG4101 reduced regulatory T cells and myeloid-derived suppressor cells and suppressed TGFβ production. In conclusion, administration of a large number of MG4101 cells was not only safe and feasible, but also exhibited efficacy in maintaining the effector arm of the host immune response. Cancer Immunol Res; 4(3); 215–24. ©2016 AACR.
