Sequential immunotherapy

Sequential immunotherapy: towards cures for autoimmunity

This Review proposes a three-step framework for immune system modulation with the goal of achieving long-term remissions in autoimmune diseases and discusses drugs for each of the steps.

  • Francisco Ramírez-Valle
  • Joseph C. Maranville
  • Robert M. Plenge
Review Article

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    • Reactive oxygen species are essential molecules that are generated and eliminated through complex balanced mechanisms. Increased reactive oxygen species levels have a role in tumour development, and targeting reactive oxygen species and their regulatory machineries is a promising therapeutic strategy. This Review discusses recent research developments in the field, their implications for cancer drug discovery, as well as emerging concepts and future perspectives.

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      • Shihua Liu
      • Peng Huang
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    • Lipid nanoparticle-based systems are increasingly being utilized for the delivery of nucleic acid-based vaccines and therapeutics. In this Perspective, Cullis and Felgner trace the evolution of these systems over the past 60 years and discuss future prospects for LNP-enabled gene therapies.

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    • In situ cancer vaccines generate tumour-specific T cell responses and hold promise for the treatment of solid tumours. This Review discusses drug delivery technologies such as lipid nanoparticles, hydrogels and scaffolds that are being developed to boost the antitumour immune effects of several types of in situ cancer vaccine.

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      • Mohamad-Gabriel Alameh
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    • Deeper pharmacological characterization of hit and lead compounds is being enabled by novel assays to characterize target behaviour as well as by advances in structural biology. This article discusses key factors in pharmacological characterization in the context of G protein-coupled receptors as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to increase the probability of them succeeding in clinical trials.

      • Terry Kenakin
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    • Advances in understanding of the cause of autoimmune diseases and clinical data from novel therapeutic modalities such as chimeric antigen receptor T cells are providing evidence that it may be possible to re-establish immune homeostasis and, potentially, prolong remission or even cure autoimmune diseases. This article proposes a three-step ‘sequential immunotherapy’ framework for immune system modulation to help achieve this ambitious goal, and discusses existing drugs and those in development for each of the three steps.

      • Francisco Ramírez-Valle
      • Joseph C. Maranville
      • Robert M. Plenge
      Review Article
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