Abstract
Vaccination for cancers arising from human papillomavirus (HPV) infection holds immense potential, yet clinical success has been elusive. Herein, we describe vaccination studies involving spherical nucleic acids (SNAs) incorporating a CpG adjuvant and a peptide antigen (E711-19) from the HPV-E7 oncoprotein. Administering the vaccine to humanized mice induced immunity-dependent on the oligonucleotide anchor chemistry (cholesterol vs (C12)9). SNAs containing a (C12)9-anchor enhanced IFN-γ production >200-fold, doubled memory CD8+ T-cell formation, and delivered more than twice the amount of oligonucleotide to lymph nodes in vivo compared to a simple admixture. Importantly, the analogous construct with a weaker cholesterol anchor performed similar to admix. Moreover, (C12)9-SNAs activated 50% more dendritic cells and generated T-cells cytotoxic toward an HPV+ cancer cell line, UM-SCC-104, with near 2-fold greater efficiency. These observations highlight the pivotal role of structural design, and specifically oligonucleotide anchoring strength (which correlates with overall construct stability), in developing efficacious therapeutic vaccines.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7629-7636 |
| Number of pages | 8 |
| Journal | Nano letters |
| Volume | 24 |
| Issue number | 25 |
| DOIs | |
| State | Published - Jun 26 2024 |
Funding
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA257926, P50CA221747, and R01CA275430. This work was also supported by the Air Force Office of Scientific Research award FA9550-22-1-0300 and the National Science Foundation grant DMR-2104353. J.H. acknowledges support from Robert H. Lurie Cancer Center\u2019s Translation Bridge Training Program at Northwestern University supported through generous philanthropy. J.D. was partially supported by a fellowship associated with the Chemistry of Life Processes Predoctoral Training Program at Northwestern University. T.O. was partially supported by a fellowship associated with the Biotechnology Training Program at Northwestern University. M.E. was partially supported by the Dr. John N. Nicholson Fellowship and the Alexander S. Onassis Public Benefit Foundation. This work made use of the IMSERC MS facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology (IIN). Imaging work was performed at the Northwestern University Center for Advanced Molecular Imaging (RRID:SCR_021192) generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Cryo-TEM imaging work made use of the BioCryo facility of Northwestern University\u2019s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-2308691). Finally, we acknowledge the Immunotherapy assessment core at the Robert H Lurie Comprehensive Cancer Center of Northwestern University, especially Dr. Surya Pandey and Li Kai for their assistance in serum cytokine analysis.
Keywords
- HPV-associated cancers
- Toll-like receptor agonist
- immunotherapeutic vaccine
- spherical nucleic acids
ASJC Scopus subject areas
- Bioengineering
- General Chemistry
- General Materials Science
- Condensed Matter Physics
- Mechanical Engineering
