Checkpoint agonist antibodies for the treatment of autoimmune disease

• Research type

  Research Study

• Full title

  Checkpoint agonist antibodies for the treatment of autoimmune disease

• IRAS ID

  300191

• Contact name

  Christopher Paluch

• Contact email

  c.paluch@gilead.com

• Sponsor organisation

  MiroBio Ltd

• Duration of Study in the UK

  4 years, 11 months, 31 days

• Research summary

  Autoimmune diseases such as psoriasis, inflammatory bowel disease and rheumatoid arthritis are caused by the inappropriate activation of the immune system against self tissue. Cells of the immune system have on their surface inhibitory receptors (also called checkpoint receptors), which have the potential to put the brakes on excessive immune responses, but in patients with autoimmunity these are not sufficiently active to halt disease. Therapeutic antibodies capable of stimulating these inhibitory receptors, and putting the brakes back on the immune system, could be used as a new type of drug to treat autoimmune disease. MiroBio is a spin-out company from Oxford University set up to develop this new class of checkpoint agonist antibody.

  In this preclinical laboratory research we will obtain (mainly via commercial suppliers) anonymised human tissues including peripheral blood immune cells (PBMCs) and biopsies of inflamed tissue from patients with autoimmune disease. Where necessary (e.g. in the study of very short-lived cells), we will use fresh blood samples donated by colleagues at MiroBio. In the laboratory we will analyse the immune cells in these tissues and use methods to activate them, in vitro and in vivo in experimental mouse models, in the presence of candidate checkpoint agonist antibodies.

  Key questions to be addressed include:
  - Can our antibodies have a meaningful effect reducing activation of human immune cells
  - Are the receptors that we are targeting present on immune cells in disease tissue
  - Which of our candidate antibodies have the most significant effects
  - Which particular types of immune cell are most affected
  - Are there particular autoimmune disease tissues which respond best to checkpoint agonists

  Theses studies will enable us to choose the best candidate drugs to take forward into later stages of development, and will guide us in choosing the most appropriate clinical indications for subsequent clinical trials.

• REC name

  London - Camberwell St Giles Research Ethics Committee

• REC reference

  21/PR/0798

• Date of REC Opinion

  8 Jun 2021

• REC opinion

  Favourable Opinion