A recent Phase 1 clinical study, published in The Lancet Haematology, evaluated the safety and efficacy of FT516, an innovative cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs).

NK cells are a component of the immune system with a key role in destroying cancer cells. FT516 was designed to express an optimized version of the CD16 protein, which enhances the ability of NK cells to eliminate tumor cells in the presence of therapeutic antibodies, such as rituximab or obinutuzumab.

Study Design

The multicenter, open-label Phase 1 study was conducted at eight research centers in the United States.
Patients, all with CD20-positive relapsed or refractory B-cell lymphoma and no other effective treatment options, received a conditioning chemotherapy regimen followed by a monoclonal antibody (rituximab or obinutuzumab) and three infusions of FT516 at escalating doses.

The infusions were accompanied by administration of IL-2, a factor that supports the survival and activity of NK cells.

Key Results

Overall, the study involved 55 adult patients, all aged 18 years or older. The highest dose tested—9 × 10⁸ cells per infusion—was well tolerated, and no cases of toxicity were observed that would limit continuation of the treatment.

Adverse events were generally manageable: only one patient (2%) developed mild (Grade 1) cytokine release syndrome, and no cases of neurotoxicity were reported. The most frequent Grade 3 or higher side effects were neutropenia (observed in 84% of patients), thrombocytopenia (36%), and anemia (27%). Importantly, no deaths were attributed to the therapy.

In terms of efficacy, the preliminary results are encouraging: 32 out of 55 patients, or 58% of the total, showed an objective response to the treatment.

Interpretation

The results indicate that iPSC-derived NK cell therapy, combined with monoclonal antibodies and IL-2, is safe and demonstrates clinical activity in relapsed or refractory B-cell lymphomas.
This approach could expand treatment options, allowing faster availability of therapies while ensuring consistent quality of the cell product. Although the data are promising, further Phase 2/3 studies will be needed to confirm efficacy and define its role in clinical practice.

Source: Strati P, Castro J, Goodman A, Bachanova V, Kamdar M, Awan FT, Solomon SR, Wong L, Wong C, Patel D, Bickers C, Zhao W, Bashir Z, Valamehr B, Elstrom RL, Patel K. 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. Lancet Haematol. 2025 Jul;12(7):e505-e515. doi: 10.1016/S2352-3026(25)00142-5. PMID: 40610174.