Exploiting RNA aptamers for cancer therapy (P4407)

TL;DRAbstract

Abstract Nucleic acid ligands (aptamers), both antagonists and agonists, can be used to target receptors on cells with high affinity and specificity. We describe the development of RNA aptamers for several cancer therapeutic applications: (1) targeting antigens to dendritic cells (DCs), (2) immune modulation, and (3) tumor-specific delivery of therapeutics. Our laboratory has successfully engineered a nuclease-resistant RNA aptamer that binds to the macrophage mannose receptor (MMR) expressed on DCs with excellent specificity and high affinity. MMR aptamer-mediated targeting of tumor antigen peptide to DCs resulted in a 4-fold increase of IFN-γ expression, which enhanced cross-presentation and T cell activation in vitro. For immune modulation of T cell function, we have now developed a human OX40 aptamer that is used as an agonist. A multimerized version of the human OX40 aptamer stimulates T cell proliferation and IFN-γ expression. Lastly, we have developed an aptamer to deliver toxic

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