Proleukin® (a modified IL-2) was the first FDA-approved cytokine used as an immunotherapeutic for renal cell carcinoma and metastatic melanoma. Although Proleukin is a potent T-cell activator, its use is associated with toxicity and induction of regulatory T cell (Treg) activation. As a result, Proleukin may trigger immunosuppression in the tumor microenvironment curtailed by Transforming Growth Factor beta (TGFβ), which would restrain ongoing anti-tumor responses.
Our technologies harness cytokines and cytokine receptors to create a multi-functional protein with potent anti-cancer properties.
FIST is a chimeric protein consisting of an IL-2 moiety fused to the extracellular domain of TGFβ receptor II (TβRII). This protein exhibits novel and potent pharmacological properties:
Modifies IL-2 receptor signalling pathway inducing robust T cells, B cells and NK cell activation.
Triggers IFNγ production in T cells, NK cells, and B cells (frequently absent in response to IL-2 stimulation).
Blocks and antagonizes TGFβ signaling pathway in lymphocytes.
Prevents Treg accumulation in tumor sites.
Disrupts tumor-induced angiogenesis (blood vessel formation).