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Efforts to treat cancer using chimeric antigen receptor (CAR)-T therapy have made astonishing progress and clinical trials against hematopoietic malignancies have demonstrated their use. However, there are still disadvantages which need to be addressed: high costs, and side effects such as Graft-versus-Host Disease (GvHD) and Cytokine Release Syndrome (CRS). Therefore, recent efforts have been made to harness the properties of certain immune cells to treat cancer—not just T cells, but also natural killer (NK) cells, macrophages (Mφ), dendritic cells (DC), etc. In this paper, we will introduce immune cell-based cellular therapies that use various immune cells and describe their characteristics and their clinical situation. The development of immune cell-based cancer therapy fully utilizing the unique advantages of each and every immune cell is expected to enhance the survival of tumor patients owing to their high efficiency and fewer side effects. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways. [ABSTRACT FROM AUTHOR]

Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy. In this review, we first summarize the roles of IL-7 and IL-7Rα and their downstream signaling pathways in immunity and cancer. Furthermore, we summarize and discuss the recent advances in the use of IL-7 and IL-7Rα as cancer immunotherapy tools and highlight their potential for therapeutic applications. This review will help in the development of cancer immunotherapy regimens based on IL-7 and IL-7Rα, and will also advance their exploitation as more effective and safe immunotherapy tools. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is an ongoing global public health threat. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and binding of the SARS-CoV-2 spike to its receptor, angiotensin-converting enzyme 2 (ACE2), on host cells is critical for viral infection. Here, we developed a luminescent biosensor that readily detects interactions of the sp ike receptor-binding domain (RBD) and ACE 2 in c ell c ulture m edium ('SpACE-CCM'), which was based on bimolecular complementation of the split nanoluciferase-fused spike RBD and ectodomain of ACE2 and further engineered to be efficiently secreted from cells by adding a heterologous secretory signal peptide (SSP). Screening of various SSPs identified 'interferon-α+alanine-aspartate' as the SSP that induced the highest activity. The SpACE-CCM biosensor was validated by observing a marked reduction of the activity caused by interaction-defective mutations or in the presence of neutralizing antibodies, recombinant decoy proteins, or peptides. Importantly, the SpACE-CCM biosensor responded well in assay-validating conditions compared with conventional cell lysate-based NanoLuc Binary Technology, indicating its advantage. We further demonstrated the biosensor's versatility by quantitatively detecting neutralizing activity in blood samples from COVID-19 patients and vaccinated individuals, discovering a small molecule interfering with the spike RBD-ACE2 interaction through high-throughput screening, and assessing the cross-reactivity of neutralizing antibodies against SARS-CoV-2 variants. Because the SpACE-CCM is a facile and rapid one-step reaction biosensor that aptly recapitulates the native spike-ACE2 interaction, it would be advantageous in many experimental and clinical applications associated with this interaction. [ABSTRACT FROM AUTHOR]

• Ginsenoside Rg3 increasd NK cell cytolytic activity. • Ginsenoside Rg3 activated NK cells through the MAPK/ERK signaling pathway. • Ginsenoside Rg3 enhanced the functional maturation of CB-derived NK cells. • Ginsenoside 20(R)-Rg3 was effective at activating NK cells and was activated through the MAPK/ERK signaling pathway. Ginseng is one of the most widely used herbal remedies for various diseases worldwide. Ginsenoside Rg3 (G-Rg3), the main component of ginseng, possesses several pharmacological properties, including anti-inflammatory, anti-tumor, antioxidant, anti-obesity, and immunomodulatory activities. However, the effect of G-Rg3 on natural killer (NK) cells in humans is not fully understood. Here, we investigated the effect of G-Rg3 on NK cell function and differentiation and elucidated the underlying mechanism. G-Rg3 increased NK cell cytotoxicity and simultaneously increased the expression of NK-activating receptors, NKp44, NKp46, and NKp30. Additionally, G-Rg3 increased the mRNA expression of NK cytolytic molecules, granzyme B and perforin. The expression of CD107a, a marker of NK cell degranulation, also increased in G-Rg3–treated NK cells. We therefore proceeded to identify which MAPK signaling pathway was involved in G-Rg3–mediated cytolytic activity. Treatment with G-Rg3 increased the phosphorylation levels of extracellular signal–regulated kinase (ERK), whereas ERK inhibition eliminated G-Rg3–induced NK cell cytotoxicity, suggesting the involvement of the ERK pathway. G-Rg3 did not affect the rate of differentiation of human cord-blood–derived NK cells; however, it increased the functional maturation of differentiated NK cells and promoted their cytotoxicity. The G-Rg3 isomer, 20(R)-Rg3, effectively activated NK cells via the extracellular signal-regulated kinase (ERK) signaling pathway, whereas 20(S)-Rg3 had no effect on NK cell activity. Altogether, the results demonstrated that 20(R)-Rg3 promoted NK cell activity via activation of the MAPK/ERK pathway, suggesting that 20(R)-Rg3 may be used as an activator of NK cell cytotoxicity for the treatment of diverse types of cancers. [ABSTRACT FROM AUTHOR]