Immune checkpoints and autoimmune diseases

In 2006, Abatacept was first approved for the treatment of RA.

In 2011, Belatacept, a derivative of Abatacept, was also approved as an immunosuppressant for kidney transplantation

In addition to Abatacept, other PD-L1-Fc fusions have also been reported

According to histological evaluation, PD-L1-Fc can significantly reduce autoantibody production and renal tubular protein deposition in lupus mouse models.

TIGIT-Fc fusion protein is another example of a soluble receptor.

Others have explored adding cytokines to the fusion protein composed of ICP ligand and Fc, an immunosuppressive protein, including CD200, Fc and TGF-β, to increase the proportion of Tregs in the spleen from 3% to more than 10%

Source Reference 1

 The humanized anti-LAG-3 agonist antibody IMP761 has immunosuppressive effects on tuberculin-induced delayed-type hypersensitivity in cynomolgus monkeys

IMP761 reduced inflammatory T cell infiltration in the DTH site to one third of the control level

The immunosuppressive effects of ICP agonist antibodies have also been confirmed in graft-versus-host disease (GVHD) and asthma models

Studies have shown that anti-VISTA agonist antibody treatment significantly prolongs the survival time of GVHD model mice.

Source Reference 1

GSK-2831781 (IMP731) is a humanized IgG1 monomer targeting LAG3.

Although GSK has terminated the Phase II clinical research project of GSK2831781 for active ulcerative enteritis, it is still carrying out further evaluation of efficacy, safety and biological mechanism to determine the next clinical development plan of GSK2831781

In addition, GSK is also developing a psoriasis indication GSK2831781, currently in Phase I stage

In the treatment of autoimmune diseases, immunosuppressive effects should be exerted in principle

However, according to the reported data of existing ICP therapies, these therapies do not seem to have serious side effects.

Experimental treatments targeting ICPs show relatively mild and acceptable side effects, and none of the various treatments described in this article have serious side effects
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Summary

In general, the development of ICP-targeted autoimmune disease therapies is still in its infancy, with fewer drugs approved for clinical use, and fewer published studies
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This situation can be attributed to many factors: greater research efforts and investment in the development of cancer treatment, the urgency of developing cancer treatment, the requirement for higher safety in the treatment of autoimmune diseases, and so on
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However, this also provides a broader vision and development space for exploring ICPs as a therapeutic target for autoimmune diseases
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In view of the potential of ICP as a therapeutic target in autoimmune diseases, it is reasonable to believe that ICPs therapy will achieve more success in the future and is expected to become a new direction in the treatment of autoimmune diseases
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references:

1.
Immune Checkpoints, a Novel Class of Therapeutic Targets for Autoimmune Diseases.
Front Immunol.
2021; 12: 645699.