TY - JOUR
T1 - Conjugation Chemistry-Dependent T-Cell Activation with Spherical Nucleic Acids
AU - Skakuj, Kacper
AU - Wang, Shuya
AU - Qin, Lei
AU - Lee, Andrew
AU - Zhang, Bin
AU - Mirkin, Chad A.
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award U54CA199091. S.W. was supported by a fellowship associated with the Chemistry of Life Processes Predoctoral Training Program T32GM105538 at Northwestern University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors also acknowledge support from the Vannevar Bush Faculty Fellowship program sponsored by the Basic Research Office of the Assistant Secretary of Defense for Research and Engineering and funded by the Office of Naval Research grant N00014-15-1-0043. The project described was also supported by the IDP Sherman Fairchild Foundation through the Robert H. Lurie Comprehensive Cancer Center, and the Prostate Cancer Foundation and Movember Foundation under award 17CHAL08
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/1/31
Y1 - 2018/1/31
N2 - Spherical nucleic acids (SNAs) can be potent sequence-specific stimulators of antigen presenting cells (APCs). When loaded with peptide antigens, they can be used to activate the immune system to train T-cells to specifically kill cancer cells. Herein, the role of peptide chemical conjugation to the DNA, which is used to load SNAs with antigens via hybridization, is explored in the context of APC activation. Importantly, though the antigen chemistry does not impede TLR-9 regulated APC activation, it significantly augments the downstream T-cell response in terms of both activation and proliferation. A comparison of three linker types, (1) noncleavable, (2) cleavable but nontraceless, and (3) traceless, reveals up to an 8-fold improvement in T-cell proliferation when the traceless linker is used. This work underscores the critical importance of the choice of conjugation chemistry in vaccine development.
AB - Spherical nucleic acids (SNAs) can be potent sequence-specific stimulators of antigen presenting cells (APCs). When loaded with peptide antigens, they can be used to activate the immune system to train T-cells to specifically kill cancer cells. Herein, the role of peptide chemical conjugation to the DNA, which is used to load SNAs with antigens via hybridization, is explored in the context of APC activation. Importantly, though the antigen chemistry does not impede TLR-9 regulated APC activation, it significantly augments the downstream T-cell response in terms of both activation and proliferation. A comparison of three linker types, (1) noncleavable, (2) cleavable but nontraceless, and (3) traceless, reveals up to an 8-fold improvement in T-cell proliferation when the traceless linker is used. This work underscores the critical importance of the choice of conjugation chemistry in vaccine development.
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U2 - 10.1021/jacs.7b12579
DO - 10.1021/jacs.7b12579
M3 - Article
C2 - 29356509
AN - SCOPUS:85041354890
SN - 0002-7863
VL - 140
SP - 1227
EP - 1230
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 4
ER -
