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Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.

Identiferoai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-10712
Date01 December 2020
CreatorsSoe, Win Mar, Lim, Joan Hui Juan, Williams, David L., Goh, Jessamine Geraldine, Tan, Zhaohong, Sam, Qi Hui, Chotirmall, Sanjay H., Ali, Nur A’Tikah Binte Mohamed, Lee, Soo Chin, Seet, Ju Ee, Ravikumar, Sharada, Chai, Louis Yi Ann
PublisherDigital Commons @ East Tennessee State University
Source SetsEast Tennessee State University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceETSU Faculty Works
Rightshttp://creativecommons.org/licenses/by/4.0/

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