Immune Check Point Modulator for Autoimmune Diseases

HLA-G2, intrinsic immune tolerant protein replacement therapy.

Advantages

  • Low risk of side effect because using intrinsic protein.
  • Modulates functions of only antigen-presenting cells.
  • Demonstrated in SLE, Allergy, Rheumatoid Arthritis models.

Background and Technology

HLA-G is secreted in placenta, and protect fetus from maternal immune system. Administration of HLA-G has proven to be effective for autoimmune diseases, and certain kinds of cancer are known to express HLA-G to avoid host immunity.

Among seven splicing variant of HLA-G, HLA-G2 is unique in the fact that it only suppresses monocytes, macrophages and dendritic cells, and does not affect T-cells, NK-cells or B-cells, which means it can remain a part of the immune system.

The researchers have demonstrated the therapeutic effect by recombinant, and PEGylated HLA-G2 in several autoimmune disease models.

Data

  • Established recombinant HLA-G2 production by E-coli expression.
  • HLA-G2 was successfully Pegylated and improved stability.
  • recombinant HLA-G2 (15µg/body) and PBS, were injected ip. twice/week for 12 weeks in SLE model mice.
  • Amount of anti-dsDNA antibodies after 72 days and urinary protein value (albumin/ creatinine) after 86 days were much lower in HLA-G2 treatment group (upper fig.).
  • H&E, PAM, PAS staining confirmed reduced infiltration of mononuclear cells and vasculitis in the kidney, as well as reduced proliferation of glomerular mesangial cells (lower Fig.).
  • PEGylated HLA-G2 increased therapeutic effects.
  • The effect was also confirmed by mouse Collagen-Induced Arthritis (CIA) model and atopic dermatitis model.
  • Proposed mechanism was confirmed by human cell analysis.10-30

Patent/Publications

PCT filed (No publications)

Researcher

Professor Katsumi Maenaka, Hokkaido University, Japan

Expectations

We are seeking a partner who could further develop and commercialize this technology. Sample for evaluation can be provided under MTA.

Product No:CD-02818

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