Hematopoietic Stem Cell- and Induced Pluripotent Stem Cell-Derived CAR-NK Cells as Reliable Cell-Based Therapy Solutions. (26th February 2021)

• Record Type: Journal Article
• Authors: Arias, Jonathan; Yu, Jingwei; Varshney, Mukesh; Inzunza, Jose; Nalvarte, Ivan
• Is Part Of: Stem cells translational medicine. Volume 10:Number 7(2021)
• Page Start: 987
• Page End: 995
• Publication Date: 2021-02-26
• Subjects: CAR-NK -- chimeric antigen receptor (CAR) -- hematopoietic stem cell (HSC) -- induced pluripotent stem (iPS) cell -- natural killer cells (NK); Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.20-0459
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Hematopoietic stem cell- (HSC) and induced pluripotent stem (iPS) cell-derived natural killer (NK) cells containing engineered functions, such as chimeric antigen receptors (CAR), offer great promise for the treatment of seemingly incurable oncological malignancies. Today, some of the main challenges of CAR cell-based therapeutics are the long manufacturing time and safety of the cell sources used. Additional challenges include avoiding graft vs host disease (GVHD) and cytokine release syndrome (CRS). Here, we show compelling evidence for the use of NK cell therapeutics as a reliable off-the-shelf option, as they address key issues. Furthermore, we highlight how iPS cells and directed differentiation toward HSC and NK cells address industrial scalability and safety. Abstract : Main areas of improvement in the creation of reliable off-the-shelf chimeric antigen receptor-natural killer (CAR-NK)-based therapies. Superdonor induced pluripotent stem (iPS) cell and hematopoietic stem cell (HSC) sources, defined xeno-free differentiation protocols, CAR genes inserted at defined genetic dose in safe harbor loci, and CAR proteins with effective on-off switch transition and endodomains.