期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：21
页码：10473-10481
DOI：10.1073/pnas.1902805116
出版社：The National Academy of Sciences of the United States of America
摘要：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.
