CAR-NK cells derived from cord blood originate mainly from CD56−CD7+CD34−HLA-DR−Lin− NK progenitor cells

Autor: Tansri Wibowo, Yosuke Kogue, Shunya Ikeda, Moto Yaga, Mana Tachikawa, Makiko Suga, Shuhei Kida, Kumi Shibata, Kazuhito Tsutsumi, Hiraku Murakami, Yasutaka Ueda, Hisashi Kato, Kentaro Fukushima, Jiro Fujita, Tomoaki Ueda, Shinsuke Kusakabe, Akihisa Hino, Michiko Ichii, Chihaya Imai, Daisuke Okuzaki, Atsushi Kumanogoh, Naoki Hosen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Therapy: Methods & Clinical Development, Vol 32, Iss 4, Pp 101374- (2024)
Druh dokumentu: article
ISSN: 2329-0501
55790224
DOI: 10.1016/j.omtm.2024.101374
Popis: Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56+ NK cells can be expanded in vitro, NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB. Here, we determined that CAR-NK cells were predominantly derived from CD56− NK progenitor cells. We first found that substantial numbers of CD19 CAR-NK cells were produced from CD56− CB mononuclear cells after in vitro culture for 2 weeks. Single-cell RNA sequencing analysis of CD56−CD3−CD14−CD19− CB mononuclear cells revealed that these cells could be subdivided into three subpopulations based on the expression of CD34 and human leukocyte antigen (HLA)-DR. NK cells originated primarily from CD34−HLA-DR− cells. In addition, among the CD34−HLA-DR− cells, only CD7+ cells could differentiate into NK cells. These results indicate that CD56−CD7+CD34−HLA-DR− lineage marker (Lin)− cells are the major origin of human CB-derived CAR-NK cells, indicating the importance of developing methods to enhance the quality and quantity of NK cells produced from these NK progenitor cells.
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