Phase I Study of Random Healthy Donor–Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors
Autor: | Sung Yoo Cho, Yong Oon Ahn, Bhumsuk Keam, Okjae Lim, Dong Wan Kim, Dae Seog Heo, Yu Kyeong Hwang, Jung Hyun Her, Tae Min Kim, Hyejin Chung, Yaewon Yang, Hana Choi, Bokyung Min, Se-Hoon Lee |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cancer Research Chemokine Lymphoma Immunology Immunotherapy Adoptive T-Lymphocytes Regulatory Disease-Free Survival 03 medical and health sciences Interleukin 21 0302 clinical medicine Immune system medicine Humans Cells Cultured biology business.industry Myeloid-Derived Suppressor Cells medicine.disease NKG2D Killer Cells Natural Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Myeloid-derived Suppressor Cell Chemokines business CD8 Progressive disease |
Zdroj: | Cancer Immunology Research. 4:215-224 |
ISSN: | 2326-6074 2326-6066 |
Popis: | 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. |
Databáze: | OpenAIRE |
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