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Initial Clinical Activity of FT596, a First-in-Class, Multi-Antigen Targeted, Off-the-Shelf, iPSC-Derived CD19 CAR NK Cell Therapy in Relapsed/Refractory B-Cell Lymphoma

Induced pluripotent stem cell (iPSC)-derived immune effector cells offer distinct advantages over existing patient- and donor-derived therapeutic approaches, including the use of a clonal master engineered iPSC line as a renewable source for the mass production of immune cells, which are available o...

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Bibliographic Details
Published in:Blood 2020-11, Vol.136 (Supplement 1), p.8-8
Main Authors: Bachanova, Veronika, Cayci, Zuzan, Lewis, Dixie, Maakaron, Joseph E., Janakiram, Murali, Bartz, Andersen, Payne, Steven, Wong, Carol, Cooley, Sarah, Valamehr, Bahram, Chu, Yu-Waye, Miller, Jeffrey S.
Format: Article
Language:English
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Summary:Induced pluripotent stem cell (iPSC)-derived immune effector cells offer distinct advantages over existing patient- and donor-derived therapeutic approaches, including the use of a clonal master engineered iPSC line as a renewable source for the mass production of immune cells, which are available off-the-shelf for broad patient access. FT596 is an investigational, off-the-shelf, multi-antigen targeting, chimeric antigen receptor (CAR) natural killer (NK) cell therapy derived from a human clonal master iPSC line engineered with three anti-tumor modalities: (1) a proprietary CD19-targeting CAR; (2) a novel high-affinity, non-cleavable CD16 Fc receptor that enables tumor targeting and enhanced antibody-dependent cell cytotoxicity in combination with a therapeutic monoclonal antibody (mAb); and (3) interleukin (IL)-15/IL-15 receptor fusion promoting cytokine-autonomous persistence. Preclinical in vivo models demonstrate potent multi-antigen targeting activity of FT596 against both CD19+ and CD19- tumor cell lines when combined with the anti-CD20 agent rituximab (Goodridge et al. 2019). FT596 is currently being investigated as a monotherapy and in combination with the anti-CD20 mAbs rituximab and obinutuzumab in a multicenter, Phase I clinical trial for the treatment of relapsed/refractory B-cell lymphoma and chronic lymphocytic leukemia. The trial will test up to four FT596 dose levels ranging from 30 to 900 million cells. We describe the demonstration of early clinical benefit of FT596 in a patient who received a single administration of FT596 as a monotherapy at the first dose level in the Phase I trial. The patient is a 76-year-old female with diffuse large B-cell lymphoma, germinal center B-cell subtype, who was initially diagnosed in January 2014. The patient received eight prior treatment regimens, including autologous stem cell transplant, rituximab in combination with engineered autologous T cells expressing antibody-coupled T-cell receptor, and, most recently, was refractory to an experimental combination therapy comprised of lymphodepleting chemotherapy followed by ex vivo expanded allogeneic NK cells, IL-2, and rituximab. The patient received fludarabine and cyclophosphamide lympho-conditioning followed by a single administration of 30 million cells of FT596 as monotherapy. During the 28-day follow-up period for safety, no dose-limiting toxicities were observed. No cytokine release syndrome, neurologic toxicity, or graft-versus-host disease of any
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2020-141606