Targeting co-stimulatory molecules in autoimmune disease

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Natalie M Edner1, Gianluca Carlesso2, James S Rush3

  • 1Institute of Immunity & Transplantation, Division of Infection & Immunity, University College London, Royal Free Campus, London, UK.

Nature Reviews. Drug Discovery
|September 17, 2020
PubMed

Insights

Targeting immune checkpoints like CTLA4 (cytotoxic T lymphocyte antigen 4) offers dual therapeutic strategies. Blocking CTLA4 treats cancer, while augmenting it helps manage autoimmune diseases by curbing immune overactivity.

Area of Science:

  • Immunology
  • Cancer Immunotherapy
  • Autoimmune Diseases

Background:

  • Immune checkpoints, including CTLA4 and PD1, are key targets in cancer immunotherapy.
  • These pathways can be modulated to control overactive immune responses in autoimmune conditions.

Purpose of the Study:

  • To review the targeting of co-stimulatory molecules for autoimmune diseases.
  • To focus on agents targeting CD28 and tumor necrosis factor receptor families.

Main Methods:

  • Review of current co-stimulatory blockade approaches.
  • Discussion of rational combinations of immune inhibitory agents.

Main Results:

  • CTLA4 activity is blocked by antibodies in cancer immunotherapy.
  • Soluble CTLA4 is provided to augment its activity in autoimmunity.
  • Co-stimulatory blockade represents a state-of-the-art approach for autoimmune diseases.

Conclusions:

  • Targeting co-stimulatory molecules offers distinct therapeutic avenues for cancer and autoimmunity.
  • Future research should explore novel combinations and address challenges in co-stimulatory blockade.

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