PI3K inhibitors to treat Cytokine Release Syndrome

Tech ID: T-019429

Technology Description

A team of researchers, led by John DiPersio and Matthew Cooper at Washington University in St. Louis, have identified a small molecule kinase inhibitor capable of mitigating cytokine release syndrome following CAR-T cell therapy. PI3K inhibitors can suppress production of IL-6 due to T cell activation without affecting the therapeutic cytotoxicity.

PI3K inhibitor suppresses IL-6 secretion by dendritic cells following activation of CAR-T cells

Cytokine release syndrome, a systemic inflammatory response, represents a significant adverse reaction to CAR-T and other adoptive cell therapies. Researchers have previously identified IL-6 as the most functionally important cytokine elevated during CRS. Since the PI3K signaling pathway regulates secretion of IL-6, PI3K inhibitors (like duvelisib) show promise to mitigate CRS without inhibiting T cell function

Stage of Research

The inventors showed that a PI3K inhibitor was able to suppress IL-6 secretion in vitro by dendritic cells or monocytes, co-cultured with CART19 cells and their targets. The CAR-T cells retained their cytotoxicity at those same concentrations of inhibitor. The same inhibition of IL-6 was seen in an immunocompetent mouse model, in which CRS was induced by in vivo administration of a T cell activating antibody.

Applications

  • Treatment for Cytokine Release Syndrome (CRS) following:
    • CAR-T cell therapy, and other adoptive cell transfer
    • Antibody therapy
    • Bispecific T-cell engager (BiTE) therapy

Key Advantages

  • Novel application of existing FDA-approved small molecule therapeutics
  • Prevents IL-6 secretion, rather than inhibiting IL-6 activity
  • Does not inhibit the anti-tumor activity of T cell therapy

Patents: Pending

Related Web Links: DiPersio Profile & Cooper Profile

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