Affiliations
- Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
PMID: 38540262 PMCID: PMC10968005 DOI: 10.3390/biomedicines12030650
Abstract
Background: NK cell exhaustion is a limitation in NK cell-based therapies. Overexpression of hTERT prevents functional exhaustion, but therapeutic safety concerns remain.
Methods: NK cells were transduced with hTERT and iCasp9 genes. Their proliferative and functional activities were compared to determine exhaustion state and transcription factor levels (EOMES and T-BET).
Results: hTERT-iCasp9-NK cells showed improved proliferation and decreased immune checkpoint molecule expression under cytokine stimulation, displaying reduced exhaustion and enhanced survival.
Conclusion: hTERT and iCasp9 can be utilized to optimize NK cell-based therapies, maintaining functionality over long-term cultivation.
Keywords: EOMES; NK cells; T-BET; exhaustion; hTERT; iCasp9; immune checkpoints; stimulation; survival.
