BACKGROUND AIMS: Natural killer (NK) cells, either naive or genetically engineered, are increasingly considered for cellular therapy of patients with malignancies. When using NK cells from peripheral blood, the number of expanded NK cells can be highly variable and the need for NK cell enrichment can make the process expensive. The NK-92 cell line (CD56+/CD3-) that was isolated from a patient with lymphoma has predictable high cytotoxic activity and can be expanded under good manufacturing practice conditions in recombinant interleukin-2. METHODS: Fifteen patients (age, 9-71 years) with advanced, treatment-resistant malignancies, either solid tumors/sarcomas (n = 13) or leukemia/lymphoma (n = 2), received two infusions of NK-92 cells, given 48 h apart. Three cohorts of patients were treated with escalating doses of NK-92 cells (n = 7 at 1 × 10(9), n = 6 at 3 × 10(9) and n = 2 at 1 × 10(10) cells/m(2)). RESULTS: No infusion-related or long-term side effects were observed. The dose of 10(10) cells/m(2) was considered the maximum expandable cell dose with the use of an established culture bag system. Three fourths of patients with lung cancer had some anti-tumor response. Only one patient of seven had development of human leukocyte antigen antibodies. The persistence of NK-92 cells (male origin) in the circulation was confirmed by Y chromosome-specific polymerase chain reaction in two female patients. CONCLUSIONS: Infusions of NK-92 cells up to 10(10) cells/m(2) were well tolerated. Despite the allogeneic nature of NK-92, development of human leukocyte antigen antibodies in these patients with cancer appears to be rare. The cells can persist in the recipient's circulation for at least 48 h. Some encouraging responses were seen in patients with advanced lung cancer.
BACKGROUND AIMS: Natural killer (NK) cells, either naive or genetically engineered, are increasingly considered for cellular therapy of patients with malignancies. When using NK cells from peripheral blood, the number of expanded NK cells can be highly variable and the need for NK cell enrichment can make the process expensive. The NK-92 cell line (CD56+/CD3-) that was isolated from a patient with lymphoma has predictable high cytotoxic activity and can be expanded under good manufacturing practice conditions in recombinant interleukin-2. METHODS: Fifteen patients (age, 9-71 years) with advanced, treatment-resistant malignancies, either solid tumors/sarcomas (n = 13) or leukemia/lymphoma (n = 2), received two infusions of NK-92 cells, given 48 h apart. Three cohorts of patients were treated with escalating doses of NK-92 cells (n = 7 at 1 × 10(9), n = 6 at 3 × 10(9) and n = 2 at 1 × 10(10) cells/m(2)). RESULTS: No infusion-related or long-term side effects were observed. The dose of 10(10) cells/m(2) was considered the maximum expandable cell dose with the use of an established culture bag system. Three fourths of patients with lung cancer had some anti-tumor response. Only one patient of seven had development of human leukocyte antigen antibodies. The persistence of NK-92 cells (male origin) in the circulation was confirmed by Y chromosome-specific polymerase chain reaction in two female patients. CONCLUSIONS: Infusions of NK-92 cells up to 10(10) cells/m(2) were well tolerated. Despite the allogeneic nature of NK-92, development of human leukocyte antigen antibodies in these patients with cancer appears to be rare. The cells can persist in the recipient's circulation for at least 48 h. Some encouraging responses were seen in patients with advanced lung cancer.
Authors: Steven N Seyedin; Jonathan E Schoenhals; Dean A Lee; Maria A Cortez; Xiaohong Wang; Sharareh Niknam; Chad Tang; David S Hong; Aung Naing; Padmanee Sharma; James P Allison; Joe Y Chang; Daniel R Gomez; John V Heymach; Ritsuko U Komaki; Laurence J Cooper; James W Welsh Journal: Immunotherapy Date: 2015-08-27 Impact factor: 4.196
Authors: Myriam N Bouchlaka; Kai D Ludwig; Jeremy W Gordon; Matthew P Kutz; Bryan P Bednarz; Sean B Fain; Christian M Capitini Journal: Oncoimmunology Date: 2016-02-18 Impact factor: 8.110