期刊
ADVANCED THERAPEUTICS
卷 3, 期 9, 页码 -出版社
WILEY
DOI: 10.1002/adtp.202000094
关键词
cancer vaccine; nanoparticles; neoantigen; papillomavirus
资金
- NIH [R01EB022563, R01CA210273, R21NS091555, R01HL134569, R01CA155010, R21CA216772, NCI-SPORE-2P50CA101942]
- MTRAC for Life Sciences Hub
- UM Forbes Institute for Cancer Discovery Pilot Grant
- Emerald Foundation
- Melanoma Research Alliance [348774]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- NSF CAREER Award [1553831]
- Broomfield International Student Fellowship
- AHA Predoctoral Fellowship [15PRE25090050, 16POST27760002]
- Parker Institute for Cancer Immunotherapy
- NIH Tetramer Core Facility [HHSN272201300006C]
- [T32 GM07767]
Potent anti-tumor T cell response and efficient intratumoral T cell infiltration are the major challenges for therapeutic cancer vaccines. To address these issues, a nanovaccine system is designed to promote anti-tumor T cell responses, and intratumoral infiltration is examined in various murine tumor models. Subcutaneous vaccination with nanodiscs carrying human papillomavirus (HPV)-16 E7 antigen elicits as high as similar to 32% E7-specific CD8 alpha+ T cell responses in circulation, representing a 29-fold improvement over the soluble peptide vaccination. Importantly, nanodisc vaccination also promotes robust intratumoral T cell infiltration and eliminates HPV16 E6/E7-expressing TC-1 tumors at mucosal sites, including lungs, inner lip, and intravaginal tissues. In a benchmark study with a live Listeria vaccine combined with anti-PD-1 IgG, nanodiscs plus anti-PD-1 immune checkpoint blockade elicits comparable levels of T cell responses with anti-tumor efficacy. Furthermore, compared with Complete Freund's Adjuvant combined with tetanus toxoid, nanodisc vaccination in HLA-A02 mice generates >200-fold stronger IFN-gamma+ T cell responses against a neoantigen from an HLA-A02 melanoma patient. Overall, these results show that the nanodisc system is a promising cancer vaccine platform for inducing anti-tumor T cell responses.
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