Immunostimulatory Spherical Nucleic Acids (IS-SNAs): Cancer Vaccines
SNAs can be designed to engage toll-like receptors (TLRs) (which control immunity in living cells) and modulate the innate immune system 10 to 100,000 times more effectively than linear nucleic acids. The nucleic acid sequences on their surfaces can be designed to stimulate or repress immune activity depending upon choice of sequence. Moreover, SNAs can be prepared to engage adaptive immunity, making the case for the field of “rational vaccinology”, where the way adjuvants and antigens are presented (i.e., the chemical structure of the conjugate) can transition a vaccine from mildly effective to curative. SNA vaccines (bearing adjuvants and antigens) have been shown to induce a significantly higher adaptive immune response than the analogous free oligonucleotides utilized in conjunction with commonly used adjuvants, ultimately leading to reduced tumor growth rates and dramatically increased survival. SNA vaccines directed towards forms of cancer are currently being validated in human clinical trials managed by Exicure (a company founded by Prof. Chad A. Mirkin) and Northwestern, respectively.
Scheme showing different SNA chemical structures that can be utilized for CpG oligonucleotide and antigen codelivery. The chemical structure of the SNA dictates the degree of immune response raised. Taken from Proc. Natl. Aca. Sci. USA, 2019, 116, 10473.