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10.1016/j.omtm.2022.04.013

http://scihub22266oqcxt.onion/10.1016/j.omtm.2022.04.013
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suck abstract from ncbi


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pmid35506060      Mol+Ther+Methods+Clin+Dev 2022 ; 25 (ä): 439-447
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  • Transcriptomic analysis reveals optimal cytokine combinations for SARS-CoV-2-specific T cell therapy products #MMPMID35506060
  • Durkee-Shock J; Lazarski CA; Jensen-Wachspress MA; Zhang A; Son A; Kankate VV; Field NE; Webber K; Lang H; Conway SR; Hanley PJ; Bollard CM; Keller MD; Schwartz DM
  • Mol Ther Methods Clin Dev 2022[Jun]; 25 (ä): 439-447 PMID35506060show ga
  • Adoptive T cell immunotherapy has been used to restore immunity against multiple viral targets in immunocompromised patients after bone-marrow transplantation and has been proposed as a strategy for preventing coronavirus 2019 (COVID-19) in this population. Ideally, expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-virus-specific T cells (CSTs) should demonstrate marked cell expansion, T cell specificity, and CD8+ T cell skewing prior to adoptive transfer. However, current methodologies using IL-4 + IL-7 result in suboptimal specificity, especially in CD8(+) cells. Using a microexpansion platform, we screened various cytokine cocktails (IL-4 + IL-7, IL-15, IL-15 + IL-4, IL-15 + IL-6, and IL-15 + IL-7) for the most favorable culture conditions. IL-15 + IL-7 optimally balanced T cell expansion, polyfunctionality, and CD8+ T cell skewing of a final therapeutic T cell product. Additionally, the transcriptomes of CD4(+) and CD8(+) T cells cultured with IL-15 + IL-7 displayed the strongest induction of antiviral type I interferon (IFN) response genes. Subsequently, microexpansion results were successfully translated to a Good Manufacturing Practice (GMP)-applicable format where IL-15 + IL-7 outperformed IL-4 + IL-7 in specificity and expansion, especially in the desirable CD8(+) T cell compartment. These results demonstrate the functional implications of IL-15-, IL-4-, and IL-7-containing cocktails for therapeutic T cell expansion, which could have broad implication for cellular therapy, and pioneer the use of RNA sequencing (RNA-seq) to guide viral-specific T cell (VST) product manufacturing.
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