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Volume 18 Issue 7, July 2019

‘Targeting trained immunity,’ inspired by the Perspective on p553.

Cover design: Susanne Harris.


  • The definition and acceptability of an orphan condition is pivotal for the assessment of European orphan medicinal product designation applications, and consequently the eligibility for incentives. Here, based on the experiences of the Committee for Orphan Medicinal Products, we discuss how to define orphan conditions in the context of the European regulatory framework.

    • Daniel J. O’Connor
    • Maria E. Sheean
    • Bruno Sepodes


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News & Analysis

  • 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.

    • Asher Mullard
  • News in Brief

  • Biobusiness Briefs

  • An Audience With

    • Merck & Co. set up its Exploratory Science Center in Cambridge, Massachusetts, to keep a finger on the pulse of emerging biological science, with a disease-agnostic scope and nimble mindset. Headed up by Daria Hazuda, CSO of the centre and vice president of infectious diseases and vaccine discovery at Merck, for now it focuses on the interaction between the microbiome and human immunity. Hazuda spoke with Asher Mullard about the firm’s exploratory science agenda, its interest in the microbiome and its continued focus on antibiotics and HIV drugs.

      • Asher Mullard
      An Audience With
  • From the Analyst's Couch

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Research Highlights

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  • 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.

    • Jennifer E. Kung
    • Natalia Jura
    Review Article
  • 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.

    • Gregory R. Steinberg
    • David Carling
    Review Article
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  • 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.

    • Willem J. M. Mulder
    • Jordi Ochando
    • Mihai G. Netea
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