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Biol Blood Marrow Transplant. 2018 Aug;24(8):1581-1589. doi: 10.1016/j.bbmt.2018.03.019. Epub 2018 Mar 27.

A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia.

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Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Electronic address:
Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Department of Hematology and Oncology, Medical University of South Carolina, Charleston, South Carolina.
Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, California.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Fortress Biotech, Inc., New York, New York.
Department of Epidemiology and Biostatistics, SUNY Downstate School of Public Health, Brooklyn New York.
Department of Hematology, Royal Free Hospital, UCL Medical School, London, United Kingdom.


Natural killer (NK) cells are an emerging immunotherapy approach to acute myeloid leukemia (AML); however, the optimal approach to activate NK cells before adoptive transfer remains unclear. Human NK cells that are primed with the CTV-1 leukemia cell line lysate CNDO-109 exhibit enhanced cytotoxicity against NK cell-resistant cell lines. To translate this finding to the clinic, CNDO-109-activated NK cells (CNDO-109-NK cells) isolated from related HLA-haploidentical donors were evaluated in a phase 1 dose-escalation trial at doses of 3 × 105 (n = 3), 1 × 106 (n = 3), and 3 × 106 (n = 6) cells/kg in patients with AML in first complete remission (CR1) at high risk for recurrence. Before CNDO-109-NK cell administration, patients were treated with lymphodepleting fludarabine/cyclophosphamide. CNDO-109-NK cells were well tolerated, and no dose-limiting toxicities were observed at the highest tested dose. The median relapse-free survival (RFS) by dose level was 105 (3 × 105), 156 (1 × 106), and 337 (3 × 106) days. Two patients remained relapse-free in post-trial follow-up, with RFS durations exceeding 42.5 months. Donor NK cell microchimerism was detected on day 7 in 10 of 12 patients, with 3 patients having evidence of donor cells on day 14 or later. This trial establishes that CNDO-109-NK cells generated from related HLA haploidentical donors, cryopreserved, and then safely administered to AML patients with transient persistence without exogenous cytokine support. Three durable complete remissions of 32.6 to 47.6+ months were observed, suggesting additional clinical investigation of CNDO-109-NK cells for patients with myeloid malignancies, alone or in combination with additional immunotherapy strategies, is warranted.


Acute myeloid leukemia; CNDO-109–activated natural killer cells

[Available on 2019-08-01]

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