Generation and Functional Characterization of Anti-CD19 Chimeric Antigen Receptor-Natural Killer Cells from Human Induced Pluripotent Stem Cells
Issued Date
2023-06-22
Resource Type
eISSN
14220067
Scopus ID
2-s2.0-85164845210
Pubmed ID
37445684
Journal Title
International journal of molecular sciences
Volume
24
Issue
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
International journal of molecular sciences Vol.24 No.13 (2023)
Suggested Citation
Klaihmon P., Kang X., Issaragrisil S., Luanpitpong S. Generation and Functional Characterization of Anti-CD19 Chimeric Antigen Receptor-Natural Killer Cells from Human Induced Pluripotent Stem Cells. International journal of molecular sciences Vol.24 No.13 (2023). doi:10.3390/ijms241310508 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88034
Title
Generation and Functional Characterization of Anti-CD19 Chimeric Antigen Receptor-Natural Killer Cells from Human Induced Pluripotent Stem Cells
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Natural killer (NK) cells are a part of innate immunity that can be activated rapidly in response to malignant transformed cells without prior sensitization. Engineering NK cells to express chimeric antigen receptors (CARs) allows them to be directed against corresponding target tumor antigens. CAR-NK cells are regarded as a promising candidate for cellular immunotherapy alternatives to conventional CAR-T cells, due to the relatively low risk of graft-versus-host disease and safer clinical profile. Human induced pluripotent stem cells (iPSCs) are a promising renewable cell source of clinical NK cells. In the present study, we successfully introduced a third-generation CAR targeting CD19, which was validated to have effective signaling domains suitable for NK cells, into umbilical cord blood NK-derived iPSCs, followed by a single-cell clone selection and thorough iPSC characterization. The established single-cell clone of CAR19-NK/iPSCs, which is highly desirable for clinical application, can be differentiated using serum- and feeder-free protocols into functional CAR19-iNK-like cells with improved anti-tumor activity against CD19-positive hematologic cancer cells when compared with wild-type (WT)-iNK-like cells. With the feasibility of being an alternative source for off-the-shelf CAR-NK cells, a library of single-cell clones of CAR-engineered NK/iPSCs targeting different tumor antigens may be created for future clinical application.