recombinant albumin-binding IL-12 SON-1010

A recombinant form of the human cytokine interleukin-12 (IL-12) conjugated to a single chain antibody fragment (scFv) targeting albumin, with potential immunomodulatory and antineoplastic activities. Upon administration, recombinant albumin-binding IL-12 SON-1010 targets and binds to serum albumin. The albumin-bound SON-1010 binds to gp60, secreted protein acidic and rich in cysteine (SPARC), and neonatal crystallizable fragment receptor (FcRn), and accumulates in the tumor microenvironment (TME). IL-12 activates the immune system by promoting the secretion of interferon-gamma (IFN-g) and activating CD8+ T cells, CD4+ T cells and natural killer cells (NKs). The activation and expansion of these immune cells mediate cytolytic immune responses against tumor cells, thereby killing tumor cells and inhibiting tumor cell proliferation. SPARC, a glycoprotein overexpressed on a variety of tumor cell types, has a high binding affinity to albumin. The gp60 receptor is overexpressed on tumor blood vessel endothelial lining, plays a key role in mediating albumin transport through blood vessels, and shares a common albumin-binding domain with SPARC. FcRn prevents the degradation and extends the half-life of albumin and albumin-bound SON-1010. The selective accumulation and extended activity of SON-1010 in the TME enhances the IL-12-mediated cytolytic responses against tumor cells while sparing the unwanted effects of systemic, peripheral immune activation. The binding to serum albumin extends circulating half-life of SON-1010.