Anti-LILRB4 Monoclonal antibody, clone AN5.2 [APC]

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent liver pathology characterized by hepatic steatosis and commonly accompanied by systematic inflammation and metabolic disorder. Despite an accumulating number of studies, no pharmacological strategy is available to treat this condition in the clinic. In this study, we applied extensive gain- and loss-of-function approaches to identify the key immune factor leukocyte immunoglobulin-like receptor B4 (LILRB4) as a negative regulator of NAFLD. The hepatocyte-specific knockout of LILRB4 (LILRB4-HKO) exacerbated high-fat diet-induced insulin resistance, glucose metabolic imbalance, hepatic lipid accumulation, and systematic inflammation in mice, whereas LILRB4 overexpression in hepatocytes showed a completely opposite phenotype relative to that of LILRB4-HKO mice when compared with their corresponding controls. Further investigations of molecular mechanisms demonstrated that LILRB4 recruits SHP1 to inhibit TRAF6 ubiquitination and subsequent inactivation of nuclear factor kappa B and mitogen-activated protein kinase cascades. From a therapeutic perspective, the overexpression of LILRB4 in a genetic model of NAFLD, ob/ob mice, largely reversed the inherent hepatic steatosis, inflammation, and metabolic disorder. Conclusion: Targeting hepatic LILRB4 to improve its expression or activation represents a promising strategy for the treatment of NAFLD as well as related liver and metabolic diseases. (Hepatology 2018;67:1303-1319)

Purpose of ReviewImmune checkpoint therapy has dramatically changed the therapeutic landscape of solid malignancies. Here, we review the scientific rationale and current data evaluating immune checkpoint inhibitors in acute myeloid leukemia (AML).Recent FindingsImmune checkpoint inhibitor monotherapy has shown limited clinical activity in AML. Initial results from early-phase clinical trials suggest that rational combinations of immune checkpoint inhibition with hypomethylating agents (HMAs) are safe and potentially more promising. There are currently no data directly comparing immune checkpoint inhibition to standard therapies. Emerging immune targets more specific for leukemia cells including LILRB4 may improve future therapeutic efficacy.SummaryThe success of immune checkpoint inhibition in AML has been modest to date. However, an improved understanding of the biology and the use of rational combinations has potential to improve rates of durable responses. Multiple clinical trials in AML are currently evaluating the use of immune checkpoints alone and in combination.