Off-the-shelf Chimeric Antigen Receptor (CAR) NK Cell Production and Application in Cancer Immunotherapy

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2022-BAO-69890
Purdue University researchers have developed an off-the-shelf treatment for targeted cancer immunotherapy. Natural killer (NK) cells are innate lymphoid cells that can be used as targeted immunotherapy for various cancers, but the lack of reliable resources for large scale production and supply of NK cells for clinical use has limited their application in cell therapy. Purdue researchers genetically engineered human pluripotent stem cells (hPSCs) that overexpress ID2, a transcription factor that greatly promotes NK cell generation, under a chemically-defined, feeder-free culture condition. The ID2-hPSC-derived NK cells contain NK cell-specific markers and show effective tumor-killing activity, comparable to NK cells derived from wild-type hPSCs. Further enhancements in antitumor activity were seen when hPSC-NK cells were engineered with a dual anti-PD-L1 CAR and universal anti-fluorescein (FITC) CAR. The use of the universal CAR design allows for targeting of solid tumors and a more widespread targeting of all cancers. The hPSC CAR-NK engineering platform provides a scalable strategy for enhanced generation of off-the-shelf NK cells for use in clinical applications for cancer treatment.

Advantages:
-Modular and scalable
-Off-the-shelf, no long waiting period for patients
-No autoimmune reactivity or cell rejection

Applications:
-Solid Tumor therapy
-Targeted immunotherapy

Publication:
Temporal Expression of Transcription Factor ID2 Improves Natural Killer Cell Differentiation from Human Pluripotent Stem Cells.
ACS Synth. Biol. 2022, 11, 6, 2001–2008
https://doi.org/10.1021/acssynbio.2c00017
Aug 17, 2022
Provisional-Patent
United States
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