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Delivering co-stimulatory tumor necrosis factor receptor agonism for cancer immunotherapy: past, current and future

Osman Dadas1, Ayse Ertay2, Mark S Cragg1,3

  • 1Antibody and Vaccine Group, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Frontiers in Immunology
|May 14, 2023
PubMed

Insights

Targeting the tumor necrosis factor superfamily (TNFSF) receptors (TNFRSF) offers promising immunotherapy strategies. This review explores their role in immune response, clinical successes, and challenges for developing next-generation immunotherapies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • The tumor necrosis factor superfamily (TNFSF) and their receptors (TNFRSF) are crucial regulators of immune cell proliferation, survival, differentiation, and function.
  • Targeting TNFRSF represents an attractive, yet under-exploited, strategy for immunotherapy development.

Purpose of the Study:

  • To review the significance of co-stimulatory TNFRSF members in generating optimal immune responses.
  • To discuss the rationale, preclinical successes, and clinical translation challenges of targeting TNFRSF for immunotherapy.
  • To evaluate current agents and explore next-generation immunostimulatory drugs.

Main Methods:

  • Literature review of studies on TNFRSF in immunotherapy.
  • Analysis of preclinical data and clinical trial outcomes.
  • Discussion of current therapeutic agents and future drug development.

Main Results:

  • Co-stimulatory TNFRSF members are vital for effective immune responses.
  • Preclinical studies show promise, but clinical translation faces hurdles.
  • Current agents have limitations, necessitating novel approaches.

Conclusions:

  • Targeting TNFRSF holds significant potential for developing potent, durable, and safe immunotherapies.
  • Overcoming clinical translation challenges is key to fully capitalizing on this receptor class.
  • Next-generation agents are being developed to address existing limitations and improve patient outcomes.
Keywords:
TNFRagonismcancerco-stimulationimmunotherapy

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