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Proc Natl Acad Sci U S A. 2019 May 21;116(21):10473-10481. doi: 10.1073/pnas.1902805116. Epub 2019 May 8.

Rational vaccinology with spherical nucleic acids.

Author information

1
Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208.
2
Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
3
Department of Chemistry, Northwestern University, Evanston, IL 60208.
4
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208.
5
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208; andrew.lee3@northwestern.edu bin.zhang@northwestern.edu chadnano@northwestern.edu.
6
Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; andrew.lee3@northwestern.edu bin.zhang@northwestern.edu chadnano@northwestern.edu.
7
Department of Chemistry, Northwestern University, Evanston, IL 60208; andrew.lee3@northwestern.edu bin.zhang@northwestern.edu chadnano@northwestern.edu.
8
International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.

Abstract

In the case of cancer immunotherapy, nanostructures are attractive because they can carry all of the necessary components of a vaccine, including both antigen and adjuvant. Herein, we explore how spherical nucleic acids (SNAs), an emerging class of nanotherapeutic materials, can be used to deliver peptide antigens and nucleic acid adjuvants to raise immune responses that kill cancer cells, reduce (or eliminate) tumor growth, and extend life in three established mouse tumor models. Three SNA structures that are compositionally nearly identical but structurally different markedly vary in their abilities to cross-prime antigen-specific CD8+ T cells and raise subsequent antitumor immune responses. Importantly, the most effective structure is the one that exhibits synchronization of maximum antigen presentation and costimulatory marker expression. In the human papillomavirus-associated TC-1 model, vaccination with this structure improved overall survival, induced the complete elimination of tumors from 30% of the mice, and conferred curative protection from tumor rechallenges, consistent with immunological memory not otherwise achievable. The antitumor effect of SNA vaccination is dependent on the method of antigen incorporation within the SNA structure, underscoring the modularity of this class of nanostructures and the potential for the deliberate design of new vaccines, thereby defining a type of rational cancer vaccinology.

KEYWORDS:

cancer vaccinology; immunotherapy; nanotechnology; spherical nucleic acids; structural design

PMID:
31068463
PMCID:
PMC6535021
[Available on 2019-11-08]
DOI:
10.1073/pnas.1902805116

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