Definition

A polypeptide nanoparticle (PNP)-based therapeutic comprised of two small interfering RNA (siRNA) oligonucleotides directed against transforming growth factor-beta 1 (TGF-beta 1) and cyclo-oxygenase-2 (COX-2), with potential immunomodulating and antineoplastic activities. Upon intravenous administration, anti-TGF-beta 1/anti-COX-2 siRNAs STP707 binds to both TGF-beta 1 and COX-2 messenger RNAs (mRNAs), preventing the translation and expression of TGF-beta 1 and COX-2 proteins. This inhibits TGF-beta 1-mediated signaling and abrogates TGF-beta 1-mediated immunosuppression, which may enhance anti-tumor immunity in the tumor microenvironment (TME) and promote a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. The inhibition of COX-2 prevents COX-2-mediated signaling, which may result in apoptosis and a reduction in tumor cell proliferation, tumor angiogenesis and metastasis.