Volume 18 Issue 7, July 2019

A long and growing list of anti-BCMA candidates — including chimeric antigen receptor-T cell therapies, antibody–drug conjugates and bispecific antibodies — are contending to transform multiple myeloma treatment.

The FDA has approved a first nanobody, lifting hopes for companies that are exploring innovative uses for domain antibodies.

Pseudokinases are key components of cellular networks, often acting as scaffolds. Many catalytically active kinases also signal through noncatalytic mechanisms in addition to their enzymatic roles. Kung and Jura discuss strategies to target pseudokinases therapeutically, as well as the progress made so far and lessons learned from inhibitors of active kinases.

AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis that is activated by physiological regulators associated with health and longevity. Here, Steinberg and Carling provide an overview of the physiological functions of AMPK and discuss the potential of this enzyme as a therapeutic target across diverse disease areas. Pharmacological activation of AMPK and the associated drug development challenges are assessed.

Cells in the innate immune system can display adaptive characteristics that lead to increased responsiveness to secondary stimulation by pathogens. This innate immune memory has been termed ‘trained immunity’. Here, Mulder and colleagues describe the mechanisms responsible for the induction of trained immunity and propose strategies to regulate it as a potential treatment of immune-related diseases.