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HLA-G platform

Harnessing the potential of a novel immune checkpoint

Invectys exploits a powerful immune checkpoint named HLA-G. It is found mostly at the fetal-maternal interface, where it has a broad action over the mother’s immune system to prevent it from destroying the fetus. It is also exploited by tumor cells to avoid being targeted by the immune system.

Invectys’ HLA-G platform currently has two products in early development, monoclonal anti-HLA-G antibodies, and a line of CAR-T cells.

I – INMAB: anti-HLA-G monoclonal antibodies

INMAB’s monoclonal antibodies are Immune Checkpoint Inhibitors (ICIs), aiming to target and disable HLA-G proteins on the surface of cancer cells. In turn, they will cancel out the suppression of the immune system by HLA-G, allowing it to attack the tumor cells.

INMAB’s capabilities will neutralize the immunosuppressive functions of HLA-G and restore immune cell functions:

  • Proliferation
  • Cytokine secretion
  • Cytotoxicity
  • Antibody secretion

HLA-G - INMAB-1

II – HLA-G therapeutic CAR-T cells

Chimeric Antigen Receptors (CARs) are artificial receptors, tailor-made to specifically target a tumor antigen expressed by a patient’s tumor cells.
In practice, T cells are first taken from a patient, and modified in the laboratory to express a CAR directed against said patient’s tumor marker.
The modified T cells (now called CAR-T cells, or CAR-Ts) are then reinjected into the patient, and will seek and destroy the cancerous cells.

CARs were first generated to bypass the intrinsic TCR specificity of T cells by providing specific antigen recognition independent of HLA-peptides complexes.
CARs graft the specificity of a monoclonal antibody onto a T cell using either sub-units derived from antibodies or antigen-binding fragments (the portion of the antibody that latches on to its antigen).

INVECTYS has generated several chimeric antigen receptors directed against HLA-G from anti-HLA-G monoclonal antibodies internally produced.

In vitro, the HLA-G CAR-Ts developed targeted all immunosuppressive HLA-G forms, either associated or not with the β2-microglobulin, and lyzed HLA-G expressing tumor cells. Invectys expects to begin clinical trials in 2020.

HLA-G - CAR-T Cells