Abstract IA16: Spherical nucleic acids as a powerful new platform for cancer immunotherapy

Abstract

Abstract Spherical nucleic acids (SNAs) are nanoparticle-oligonucleotide conjugates characterized by a dense, spherical shell of radially oriented oligonucleotides. SNAs enter cells without the need for auxiliary transfection reagents, are more resistant to nuclease degradation than their linear counterparts, and show minimal toxicity and off-target immunogenicity. These emergent properties of the SNA platform enable the design of powerful immunotherapy agents against cancer cells. The SNA platform allows simultaneous delivery of Toll-like receptor (TLR) agonist oligonucleotides and cancer-associated antigen peptides to antigen-presenting cells (APCs). The oligonucleotides on the surface of the SNAs activate of the innate immune system through TLRs to mature the APCs, which in turn activates effector immune cells to target cell displaying the cancer-associated peptide. Compared to mixtures of free peptides and oligonucleotides, SNAs exhibit up to 80-fold increase in potency, 400-fold higher cellular response to antigens and improve median survival in mice with lymphomas through antigen-specific targeting of cancer cells. The enhancement of the immune properties arises from a combination of increase in cellular uptake, polyvalent binding of SNAs to TLRs and the co-delivery of the TLR agonist oligonucleotides and peptide to the same cell. Additionally, the SNA architecture enables the control of oligonucleotide to peptide ratio, subcellular release location of the peptide and release kinetics. Combined with their high serum stability, at-scale synthesis and minimal toxicity profile, SNAs hold great promise for the development of cancer vaccines. Citation Format: Chad A. Mirkin. Spherical nucleic acids as a powerful new platform for cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA16.