期刊
JOURNAL OF CONTROLLED RELEASE
卷 337, 期 -, 页码 168-178出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.07.026
关键词
adjuvant; vaccine; nanoparticle; cancer immunotherapy; TLR agonist
资金
- NIH [R01EB022563, R01CA21 0273, R01AI127070, R01DK125087, R01DE030691, R21NS091555, R01NS122536, R01HL134569]
- NSF CAREER Award [1553831]
- NSERC
- CIHR
- Cancer Center Support Grant [P30 CA046592]
- NIH Tetramer Core Facility [HHSN272201300006C]
This study confirmed that sHDL combined with polyICLC is a strong vaccine platform for inducing CD8+ T cell responses. While the CpG B and CpG C classes generated strong responses in mice, their efficacy was mixed in non-human primates.
Conventional cancer vaccines based on soluble vaccines and traditional adjuvants have produced suboptimal therapeutic efficacy in clinical trials. Thus, there is an urgent need for vaccine technologies that can generate potent T cell responses with strong anti-tumor efficacy. We have previously reported the development of synthetic high-density protein (sHDL) nanodiscs for efficient lymph node (LN)-targeted co-delivery of antigen peptides and CpG oligonucleotides (a Toll-like receptor-9 agonist). Here, we performed a comparative study in mice and non-human primates (NHPs) to identify an ideal vaccine platform for induction of CD8+ T cell responses. In particular, we compared the efficacy of CpG class B, CpG class C, and polyICLC (a synthetic double-stranded RNA analog, a TLR-3 agonist), each formulated with antigen-carrying sHDL nanodiscs. Here, we report that sHDL-Ag admixed with polyICLC elicited robust Ag-specific CD8+ T cell responses in mice, and when used in combination with alpha-PD-1 immune checkpoint inhibitor, sHDL-Ag + polyICLC eliminated large established (similar to 100 mm(3)) MC-38 tumors in mice. Moreover, sHDL-Gag + polyICLC induced robust Simian immunodeficiency virus Gag-specific, polyfunctional CD8+ T cell responses in rhesus macaques and could further amplify the efficacy of recombinant adenovirus-based vaccine. Notably, while both sHDL-Ag-CpG-B and sHDL-Ag-CpG-C generated strong Ag-specific CD8+ T cell responses in mice, their results were mixed in NHPs. Overall, sHDL combined with polyICLC offers a strong platform to induce CD8+ T cells for vaccine applications.
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