title: Phase I Study of Random Healthy Donor-Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors.
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 × 10(7) 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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yaewon
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Okjae
authors.initials: O
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. gabriel9@snu.ac.kr ykhwang@mogam.re.kr.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong-Oon
authors.initials: YO
authors.lastname: Ahn
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Choi
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Chung
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Min
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Her
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea.
authors.forename: Sung Yoo
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Cell Therapy Team, MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Korea. gabriel9@snu.ac.kr ykhwang@mogam.re.kr.
authors.forename: Yu Kyeong
authors.initials: YK
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood; D018572:Disease-Free Survival; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018925:Chemokines