Definition

A synthetic microRNA (miRNA) mimic of the endogenous tumor suppressor miR-193a-3p formulated in lipid nanoparticles (LNPs), with potential antineoplastic and immune-activating activities. Upon administration, miRNA-193a-3p mimic INT-1B3 targets tumor cells, binds to its target sequence in mRNA transcripts, which leads to translational repression or mRNA degradation. This inhibits protein expression encoded by that particular mRNA sequence. INT-1B3 is able to downregulate many oncogenic signaling pathways, such as the oncogenic PI3K/Akt and Ras/MAPK pathways, and upregulate the tumor suppressive PTEN pathway. INT-1B3 also modulates the expression of cyclin D1, Mcl-1, K-Ras, c-Kit and TIM-3. In addition, INT-1B3 is able to modulate the tumor microenvironment (TME) through inhibition of CD39/CD73 and by downregulating the adenosine-A2A receptor pathway. This leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), increases the maturation of dendritic cells (DCs) and induces a T cell-mediated anti-tumor immune response. Altogether, this may induce cell cycle arrest and apoptosis, increase cell senescence, and decrease tumor cell proliferation, survival, migration and metastasis.