Aptamer-Based Multispecific Therapeutic Agents

Abstract

Engineered multispecific antigen binding molecules are provided which contain two or more different aptamer moieties joined by a linker. The antigen binding molecules are capable of specifically binding to one or more antigens and bridging different cell types, such as immune cells and cancer cells. The linked aptamers can be used to modulate and enhance immune function.

What is claimed is: 
     
         1 . An aptamer-based multispecific antigen binding molecule comprising 1) two or more target binding aptamer regions having binding specificities for different targets, and 2) one or more linkers connecting the aptamer regions, wherein the linker comprises a click chemistry product. 
     
     
         2 . The aptamer-based multispecific antigen binding molecule of  claim 1 , wherein the linker further comprises a linker moiety selected from the group consisting of a covalent bond, a single-stranded nucleic acid, a double-stranded nucleic acid, self-assembling complementary oligonucleotides, a peptide, a polypeptide, an oligosaccharide, a polysaccharide, a synthetic polymer, a hydrazone, a thioether, an ester, a triazole, a nanoparticle, a micelle, a liposome, a cell, and combinations thereof. 
     
     
         3 . The aptamer-based multispecific antigen binding molecule of any of the preceding claims that can bind to specific targets on one or more of human cells, immune cells, cancer cells, genetically modified cells, bacteria, or viruses. 
     
     
         4 . The aptamer-based multispecific antigen binding molecule of any of the preceding claims that can redirect the binding of one cell type from one target cell to another target cell. 
     
     
         5 . The aptamer-based multispecific antigen binding molecule of any of the preceding claims that can form a bridge between an immune cell and a cancer cell. 
     
     
         6 . The aptamer-based multispecific antigen binding molecule of any of the preceding claims that can stimulate and activate an immune cell. 
     
     
         7 . The aptamer-based multispecific antigen binding molecule of  claim 6 , wherein the immune cell is a T-cell, NK-cell, or macrophage, and said binding leads to destruction of a target cell bound to a target binding aptamer of the aptamer based multispecific antigen binding molecule. 
     
     
         8 . The aptamer-based multispecific antigen binding molecule of any of the preceding claims, wherein the molecule possesses a binding specificity for an antigen selected from the group consisting of CD3, CD8, CD4, CD19, Epithelial cell adhesion molecule, CD20, CD22, CD123, BCMA, B7H3, CEA, PSMA, Her2, CD33, CD38, DLL3, EGF-R, NKG2D ligands, MHC class I-related protein MR1, mesothelin, PD-1, PD-L1, CTLA04, Lag-3, TIM-3, OX40, CD47, VEGF, PRAME, NY-ESO-1, MAGE A4, MAGE A3/A6, MAGE A10, and AFP. 
     
     
         9 . The aptamer-based multispecific antigen binding molecule of  claim 3 , wherein the molecule binds to an immune cell expressing CD3 antigen. 
     
     
         10 . The aptamer-based multispecific antigen binding molecule of  claim 1 , wherein the molecule binds PSMA antigen on a cancer cell. 
     
     
         11 . The aptamer-based multispecific antigen binding molecule of  claim 1  comprising one or more CD3 antigen binding region that can bind to a T-cell and one or more PSMA antigen binding region that can bind to a PSMA expressing cell, wherein the CD3 antigen binding region and the PMSA antigen binding region are connected by one or more linkers. 
     
     
         12 . Use of the aptamer-based multispecific antigen binding molecule of  claim 11  in the treatment of a PSMA expressing cancer including prostate cancer.