Anti-CD4 monoclonal antibody(Immunotech)

Numerous studies have highlighted the role of translationally controlled tumor protein (TCTP) as a key inflammatory mediator of asthma and allergies. Our previous study revealed that blocking the cytokine-like activity of TCTP using JEW-M449, an anti-TCTP monoclonal antibody (mAb), alleviated allergic inflammation in asthmatic mice. This study aimed to determine whether directly delivering JEW-M449 into the respiratory tract is a more effective way of mitigating airway inflammation in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation than delivering this antibody via the intraperitoneal (IP) route. OVA-sensitized mice were intranasally administered JEW-M449 to enable its direct delivery to the respiratory tract before OVA challenge. We evaluated the changes in the levels of bronchoalveolar lavage fluid (BALF) cells, T helper type 2 (Th2) cytokines, OVA-specific immunoglobulin E (IgE), and histopathological alterations in the lung tissues. Intranasal (IN) administration of JEW-M449 significantly ameliorated the pathological changes associated with OVA-induced lung injury, including reduced inflammatory cell infiltration and mucus hypersecretion. Mice IN administered JEW-M449 also showed decreased OVA-mediated induction of Th2 cytokines in BALF and lung homogenates. Importantly, JEW-M449 delivered via the IN route reached the lung tissue more effectively and exerted superior anti-inflammatory effects in OVA-challenged mice than the IP-delivered JEW-M449. This study is the first to demonstrate the efficacy of directly delivering JEW-M449 anti-TCTP mAb into the respiratory tract to alleviate the asthma phenotype in a mouse model, thereby highlighting a potential delivery strategy for novel inhaled mAb therapeutics for human asthma.

S100A4 is a DAMP protein. S100A4 is overexpressed in patients with systemic sclerosis (SSc), and levels correlate with organ involvement and disease activity. S100A4−/− mice are protected from fibrosis. The aim of this study was to assess the antifibrotic effects of anti‐S100A4 monoclonal antibody (mAb) in murine models of SSc and in precision cut skin slices of patients with SSc.

The effects of anti‐S100A4 mAbs were evaluated in a bleomycin‐induced skin fibrosis model and in Tsk‐1 mice with a therapeutic dosing regimen. In addition, the effects of anti‐S100A4 mAbs on precision cut SSc skin slices were analyzed by RNA sequencing.

Inhibition of S100A4 was effective in the treatment of pre‐established bleomycin‐induced skin fibrosis and in regression of pre‐established fibrosis with reduced dermal thickening, myofibroblast counts, and collagen accumulation. Transcriptional profiling demonstrated targeting of multiple profibrotic and proinflammatory processes relevant to the pathogenesis of SSc on targeted S100A4 inhibition in a bleomycin‐induced skin fibrosis model. Moreover, targeted S100A4 inhibition also modulated inflammation‐ and fibrosis‐relevant gene sets in precision cut SSc skin slices in an ex vivo trial approach. Selected downstream targets of S100A4, such as AMP‐activated protein kinase, calsequestrin‐1, and phosphorylated STAT3, were validated on the protein level, and STAT3 inhibition was shown to prevent the profibrotic effects of S100A4 on fibroblasts in human skin.

Inhibition of S100A4 confers dual targeting of inflammatory and fibrotic pathways in complementary mouse models of fibrosis and in SSc skin. These effects support the further development of anti‐S100A4 mAbs as disease‐modifying targeted therapies for SSc.