| RRC ID |
88212
|
| Author |
Nakamura N, Liao J, Soda Y, Takahashi M, Kodera H, Kobari Y, Hirai Y, Takaori-Kondo A, Okada T.
|
| Title |
Optimizing activation and culture conditions for the production of cord blood-derived CAR-T and natural killer cells.
|
| Journal |
Br J Haematol
|
| Abstract |
Cord blood (CB) is gaining attention as a source of chimeric antigen receptor (CAR) T/NK cells. Many studies have focused on the therapeutic effects, but the methods of activating and culturing T/NK cells without excessive exhaustion during the initial stages of the production of CB-derived CAR-T/NK cells are yet to be established. The activation and culture conditions developed for peripheral blood (PB) CAR-T/NK cells have been used for CB-CAR-T/NK cells, but there are differences in the composition and maturity of PB and CB lymphocytes. Thus, this study aims to optimize activation and culture conditions for the production of CB-CAR-T/NK cells. We compared different doses of various cytokines and found that the balance between activation and exhaustion was best with stimulation with a CD3/CD28 agonist followed by 40 U/mL interleukin (IL)-7+ 40 U/mL IL-15 for PB-T cells; 40 U/mL IL-2+ 40 U/mL IL-7+ 40 U/mL IL-15 for CB-T cells; 40 U/mL IL-2+ 40 U/mL IL-15 for PB-NK cells; and 40 U/mL IL-2+ 200 U/mL IL-15 for CB-NK cells. Using killing assays, we confirmed that these cytokine protocols improved the anti-tumour effects. These results will be useful for the development of CB-CAR-T/NK-cell therapies and suggest the potential of these modalities.
|
| Volume |
207(5)
|
| Pages |
1863-1873
|
| Published |
2025-11-1
|
| DOI |
10.1111/bjh.70139
|
| PMID |
41030086
|
| PMC |
PMC12624202
|
| MeSH |
Cell Culture Techniques* / methods
Cells, Cultured
Cytokines / pharmacology
Fetal Blood* / cytology
Fetal Blood* / immunology
Humans
Immunotherapy, Adoptive* / methods
Interleukin-15 / pharmacology
Killer Cells, Natural* / cytology
Killer Cells, Natural* / immunology
Killer Cells, Natural* / metabolism
Lymphocyte Activation*
Receptors, Chimeric Antigen* / immunology
Receptors, Chimeric Antigen* / metabolism
T-Lymphocytes* / cytology
T-Lymphocytes* / immunology
|
| IF |
5.206
|
| Resource |
| Cord blood stem cells for research |
|
