Off-the-shelf induced pluripotent stem-cell-derived natural killer-cell therapy in relapsed or refractory B-cell lymphoma: a multicentre, open-label, phase 1 study.
Publication Title
Lancet Haematol
Document Type
Article
Publication Date
7-1-2025
Keywords
Humans; Male; Female; Middle Aged; Aged; Adult; Lymphoma, B-Cell; Killer Cells, Natural; Recurrence; Antineoplastic Combined Chemotherapy Protocols; washington; swedish
Abstract
BACKGROUND: Natural killer-cell therapies are limited by donor cell sourcing and dose-to-dose variability. FT516 is an induced pluripotent stem cell (iPSC)-derived natural killer-cell therapy expressing high-affinity, non-cleavable CD16 to optimise antibody-dependent cellular cytotoxicity in combination with therapeutic monoclonal antibody. We aimed to assess the safety of FT516 in patients with relapsed or refractory B-cell lymphoma.
METHODS: This multicentre, open-label, phase 1 study was conducted at eight research centres in the USA. Eligible patients were aged 18 years or older, had B-cell lymphoma expected to express CD20, with relapsed or refractory disease following at least one previous systemic therapy including anti-CD20 antibody, had measurable disease, and had no treatment options expected to improve survival. Participants received fludarabine (30 mg/m
FINDINGS: From Oct 11, 2019, to Nov 28, 2022, 56 patients were enrolled, 55 of whom received FT516. 32 (58%) patients were male, 23 (42%) were female, and 43 (78%) were White. The maximum FT516 cell dose (9 × 10
INTERPRETATION: Our findings suggest that cell therapy using iPSC-derived, gene-modified natural killer cells in combination with monoclonal antibody and IL-2 is safe and active in B-cell malignancies and might address limitations of currently available immune-cell therapies, including manufacturing time, heterogeneity, access, and cost.
FUNDING: Fate Therapeutics.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Hematology
DOI
10.1016/S2352-3026(25)00142-5
