Dual-targeting CD33/CD123 NANOBODY T-cell engager with potent anti-AML activity and good safety profile.

Novel therapies are needed for effective treatment of acute myeloid leukemia (AML). Relapse is common and salvage treatment with cytotoxic chemotherapy is rarely curative. CD123 and CD33, 2 clinically validated targets in AML, are jointly expressed on blasts and leukemic stem cells in >95% of patients with AML.

Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8.

A detrimental role for matrix metalloproteinase 8 (MMP8) has been identified in several pathological conditions, e.g., lethal hepatitis and the systemic inflammatory response syndrome.

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF.

Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis.

Matrix metalloprotease 8-dependent extracellular matrix cleavage at the blood-CSF barrier contributes to lethality during systemic inflammatory diseases.

Systemic inflammatory response syndrome (SIRS) is a highly mortal inflammatory disease, associated with systemic inflammation and organ dysfunction. SIRS can have a sterile cause or can be initiated by an infection, called sepsis. The prevalence is high, and available treatments are ineffective and mainly supportive.

Matrix metalloproteinases as drug targets in ischemia/reperfusion injury.

Deficient blood supply (ischemia) is a common consequence of some surgical procedures and certain pathologies. Once blood circulation is re-established (reperfusion), a complex series of events results in recruitment of inflammatory cells, rearrangement of the extracellular matrix and induction of cell death, which lead to organ dysfunction. Although ischemia/reperfusion (I/R) injury is an important cause of death, there is no effective therapy targeting the molecular mechanism of disease progression.

Matrix metalloproteinase8 has a central role in inflammatory disorders and cancer progression.

The predominant role of matrix metalloproteinase 8 in extracellular matrix turnover, modulation of inflammatory responses and other physiological processes is well documented. Several recent studies highlight the involvement of MMP8 in a wide range of pathologies. This review will shed light on the putative role of MMP8 as a drug target or disease marker in some inflammatory disorders and in cancer progression.

Cecal ligation and puncture: the gold standard model for polymicrobial sepsis?

Sepsis is a serious medical condition characterized by dysregulated systemic inflammatory responses followed by immunosuppression. To study the pathophysiology of sepsis, diverse animal models have been developed. Polymicrobial sepsis induced by cecal ligation and puncture (CLP) is the most frequently used model because it closely resembles the progression and characteristics of human sepsis.

Type I interferon drives tumor necrosis factor-induced lethal shock.

Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases.