Dr Jode Goodridge (Fate Therapeutics, USA) described the chimeric antigen receptor (CAR)-induced natural killer cell product, referred to as FT596 [1]. The FT596 platform circumvents some of the hurdles posed by conventional CAR19 T-cell therapy, such as product heterogeneity, and persistence of effect. Producing FT596 begins with human iPSCs that are capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. The iPSCs are genetically engineered, after which a single clone is selected and grown in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells, such as natural killer and T cells.
The researchers modified FT596 to carry a CAR targeting the CD19 protein, as well as CD16, which boosts and broadens the natural killer cellsâ ability to kill cancer cells, and IL-15, which stimulates FT596 to proliferate and persist.
To test it in vitro, the researchers used CD19+ CD20+ B lymphoblast target cells to demonstrate that the anti-tumour activity of FT596 is roughly comparable with the activity of primary CD19-targeted CAR T cells. When combined with the anti-CD20 monoclonal rituximab, activity was even more effective at eliminating CD19- CD20+ B lymphoblast target cells than the monoclonal antibody alone (64% vs 30% clearance, respectively, at 36 hours).
In vivo, the researchers used mouse models with B-cell malignancy to demonstrate that FT596 was superior at eradicating B-cell lymphoma, compared with mice treated with induced natural killer cells alone or induced natural killer cells modified with CD19-CAR alone (P<0.002).
Dr Goodridge: âFrom 106 iPSCs, we can generate 1011 to 1012 induced natural killer cells at a 100-litre scale, and the output is continuous.â The cost of treatment with FT596 is about $2,500. First-in-human studies have yet to report.
1. Goodridge J, et al. Abstract 301, ASH 2019, 7-10 December, Orlando, USA.
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Table of Contents: ASH 2019
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