Drug targeting to the tumor microenvironment

Although up to 80% of cells in a tumor mass are nonmalignant (e.g. cancer associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), T cells, and endothelial cells), they are still critical to cancer cell growth and proliferation. We have designed and synthesized a toolbox of targeting ligands that bind selectively to each of these different stromal cell types. We have then exploited these cell-specific ligands to deliver attached therapeutic agents very specifically to desired stromal cell types in solid tumors. Depending on the specific objective, we have been able to develop targeted drugs that can either kill, inactivate, proliferate or reprogram each of the above stromal cell types in a highly selective manner. Because these stromal cells are not mutating and since they are present in virtually all solid tumors, they constitute excellent targets for creation of broadly applicable therapies for many cancers.