tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2022 Apr 11;1-9.
doi: 10.1080/21645515.2022.2055945. Online ahead of print.
Human placental hematopoietic stem cell derived natural killer cells (CYNK-001) mediate protection against influenza a viral infection
Joseph Gleason[SUP] 1 [/SUP], Yuechao Zhao[SUP] 1 [/SUP], Irene Raitman[SUP] 1 [/SUP], Lin Kang[SUP] 1 [/SUP], Shuyang He[SUP] 1 [/SUP], Robert Hariri[SUP] 1 [/SUP]
Affiliations
Abstract
Influenza A virus (IAV) infections are associated with a high healthcare burden around the world and there is an urgent need to develop more effective therapies. Natural killer (NK) cells have been shown to play a pivotal role in reducing IAV-induced pulmonary infections in preclinical models; however, little is known about the therapeutic potential of adoptively transferred NK cells for IAV infections. Here, we investigated the effects of CYNK-001, human placental hematopoietic stem cell derived NK cells that exhibited strong cytolytic activity against a range of malignant cells and expressed high levels of activating receptors, against IAV infections. In a severe IAV-induced acute lung injury model, mice treated with CYNK-001 showed a milder body weight loss and clinical symptoms, which led to a delayed onset of mortality, thus demonstrating their antiviral protection in vivo. Analysis of bronchoalveolar lavage fluid (BALF) revealed that CYNK-001 reduced proinflammatory cytokines and chemokines highlighting CYNK-001's anti-inflammatory actions in viral induced-lung injury. Furthermore, CYNK-001-treated mice had altered immune responses to IAV with reduced number of neutrophils in BALF yet increased number of CD8+ T cells in the BALF and lung compared to vehicle-treated mice. Our results demonstrate that CYNK-001 displays protective functions against IAV via its anti-inflammatory and immunomodulating activities, which leads to alleviation of disease burden and progression in a severe IAV-infected mice model. The potential of adoptive NK therapy for IAV infections warrants clinical investigation.
Keywords: Virus; inflammation; influenza a; natural killer cells.
. 2022 Apr 11;1-9.
doi: 10.1080/21645515.2022.2055945. Online ahead of print.
Human placental hematopoietic stem cell derived natural killer cells (CYNK-001) mediate protection against influenza a viral infection
Joseph Gleason[SUP] 1 [/SUP], Yuechao Zhao[SUP] 1 [/SUP], Irene Raitman[SUP] 1 [/SUP], Lin Kang[SUP] 1 [/SUP], Shuyang He[SUP] 1 [/SUP], Robert Hariri[SUP] 1 [/SUP]
Affiliations
- PMID: 35404743
- DOI: 10.1080/21645515.2022.2055945
Abstract
Influenza A virus (IAV) infections are associated with a high healthcare burden around the world and there is an urgent need to develop more effective therapies. Natural killer (NK) cells have been shown to play a pivotal role in reducing IAV-induced pulmonary infections in preclinical models; however, little is known about the therapeutic potential of adoptively transferred NK cells for IAV infections. Here, we investigated the effects of CYNK-001, human placental hematopoietic stem cell derived NK cells that exhibited strong cytolytic activity against a range of malignant cells and expressed high levels of activating receptors, against IAV infections. In a severe IAV-induced acute lung injury model, mice treated with CYNK-001 showed a milder body weight loss and clinical symptoms, which led to a delayed onset of mortality, thus demonstrating their antiviral protection in vivo. Analysis of bronchoalveolar lavage fluid (BALF) revealed that CYNK-001 reduced proinflammatory cytokines and chemokines highlighting CYNK-001's anti-inflammatory actions in viral induced-lung injury. Furthermore, CYNK-001-treated mice had altered immune responses to IAV with reduced number of neutrophils in BALF yet increased number of CD8+ T cells in the BALF and lung compared to vehicle-treated mice. Our results demonstrate that CYNK-001 displays protective functions against IAV via its anti-inflammatory and immunomodulating activities, which leads to alleviation of disease burden and progression in a severe IAV-infected mice model. The potential of adoptive NK therapy for IAV infections warrants clinical investigation.
Keywords: Virus; inflammation; influenza a; natural killer cells.