Establishment of a protocol for rapidly expanding Epstein–Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity

Autor: Chih-Hao Fang, Ya Fang Cheng, Shian-Ren Lin, Wan-Yu Lai, Li-Ren Liao, Yen-Ling Chiu, Jan-Mou Lee
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Cancer, Vol 24, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-024-12707-7
Popis: Abstract Background Lytic Epstein–Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs. Methods By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs. Results When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs. Conclusion We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.
Databáze: Directory of Open Access Journals
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