Reducing XXXX of Immune Therapy Using Aptamer-Targeted Drug Delivery.

@entity5 @entity1 @entity137 @entity19
Modulating the function of immune receptors with antibodies is ushering in a new era in @entity5 immunotherapy. With the notable exception of PD-1 blockade used as monotherapy, immune modulation can be associated with significant @entity137 that are expected to escalate with the development of increasingly potent immune therapies. A general way to reduce @entity137 is to target immune potentiating drugs to the @entity5 or immune cells of the @entity1 . This Crossroads article discusses a new class of nucleic acid-based immune-modulatory drugs that are targeted to the @entity5 or to the immune system by conjugation to oligonucleotide aptamer ligands. Cell-free chemically synthesized short oligonucleotide aptamers represent a novel and emerging platform technology for generating ligands with desired specificity that offer exceptional versatility and feasibility in terms of development, manufacture, and conjugation to an oligonucleotide cargo. In proof-of-concept studies, aptamer ligands were used to target immune-modulatory siRNAs or aptamers to induce neoantigens in the @entity5 cells, limit costimulation to the @entity5 lesion, or enhance the persistence of vaccine-induced immunity. Using increasingly relevant @entity19 models, the aptamer-targeted immune-modulatory drugs engendered protective antitumor immunity that was superior to that of current "gold-standard" therapies in terms of efficacy and lack of @entity137 or reduced @entity137 . To overcome immune exhaustion aptamer-targeted siRNA conjugates could be used to downregulate intracellular mediators of exhaustion that integrate signals from multiple inhibitory receptors. Recent advances in aptamer development and second-generation aptamer-drug conjugates suggest that we have only scratched the surface. Cancer Immunol Res; 3(11); 1195-200.   2015 AACR.
