PD-1 antibody interactions with Fc gamma receptors enable PD-1 agonism to inhibit T cell activation - therapeutic implications for autoimmunity.

PD-1 has emerged as a central inhibitory checkpoint receptor in maintaining immune homeostasis and as a target in cancer immunotherapies. However, targeting PD-1 for the treatment of autoimmune diseases has been more challenging. We recently showed in a phase 2a trial that PD-1 could be stimulated with the PD-1 agonist antibody peresolimab to treat rheumatoid arthritis.

LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth.

Purpose: MET, the receptor for hepatocyte growth factor (HGF), has been implicated in driving tumor proliferation and metastasis. High MET expression is correlated with poor prognosis in multiple cancers. Activation of MET can be induced either by HGF-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional upregulation or by HGF-dependent autocrine or paracrine mechanisms.

Immunohistochemical application of a highly sensitive and specific murine monoclonal antibody recognising the extracellular domain of the human hepatocyte growth factor receptor (MET).

Aims: Development of novel targeted therapies directed against hepatocyte growth factor (HGF) or its receptor (MET) necessitates the availability of quality diagnostics to facilitate their safe and effective use. Limitations of some commercially available anti-MET antibodies have prompted development of the highly sensitive and specific clone A2H2-3. Here we report its analytical properties when applied by an automated immunohistochemistry method.

Fas ligand-induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogue.

Fas ligand (FasL)-induced lung inflammation has recently been suggested to play an important role in the pathogenesis of acute respiratory disease syndrome (ARDS). In order to further explore this connection, we established a FasL-induced murine model of pulmonary inflammation. Instillation of recombinant FasL (rFasL) into the lung induced neutrophil infiltration and increased pulmonary permeability, as evidenced by increased total protein in the airspace; both occur in patients with ARDS.

CtrA mediates a DNA replication checkpoint that prevents cell division in Caulobacter crescentus.

Coordination of DNA replication and cell division is essential in order to ensure that progeny cells inherit a full copy of the genome. Caulobacter crescentus divides asymmetrically to produce a non-replicating swarmer cell and a replicating stalked cell. The global response regulator CtrA coordinates DNA replication and cell division by repressing replication initiation and transcription of the early cell division gene ftsZ in swarmer cells.