Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target cytotoxic agents to TLR9-expressing malignant cells are disclosed. Compositions and methods are disclosed for targeted treatment of cancer or cancer-stem cells with extracellular TLR9 expression, such as primary human MDS progenitors and hematopoietic stem cell (HSC). In particular, molecules containing TLR9 targeting ligands that target cytotoxic agents to TLR9-expressing malignant cells are disclosed.
