Large-scale generation of iNK and CAR-iNK cells from CD34+ haematopoietic stem and progenitor cells for adoptive immunotherapy
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'une approche méthodologique pour générer à grande échelle des cellules NK induites (iNK) et des lymphocytes CAR-iNK à partir de cellules souches et de cellules progénitrices hématopoïétiques CD34+ issues du sang ombilical humain
Chimaeric antigen receptor (CAR) natural killer (CAR-NK) cells are a promising alternative to CAR-T cells for immunotherapies. High and multiple doses of CAR-NK cell infusions are essential to maintain therapeutic efficacy in clinical trials, requiring efficient methods for generating CAR-NK cells at scale. Here we develop a three-step strategy to generate high yields of induced NK (iNK) and CAR-iNK cells from human umbilical cord blood CD34+ haematopoietic stem and progenitor cells (CD34+ HSPCs). Starting from a single umbilical cord blood unit of CD34+ HSPCs, our method produces 14–83 million mature iNK cells or 7–32 million CAR-iNK cells with high expression levels of CD16 and CAR and undetectable T-cell contamination. Both fresh and thawed iNK and CAR-iNK cells demonstrate anti-tumour activities against various human cancer cells and prolong the survival of human tumour-bearing animals. The high yields of CAR-NK cells and reduced costs of our method’s CAR engineering support the broad applications of these cells for treating cancer patients.
Nature Biomedical Engineering , résumé, 2025