DNA Anchoring Strength Directly Correlates with Spherical Nucleic Acid-Based HPV E7 Cancer Vaccine Potency

Jeongmin Hwang, Jasper Wilson Dittmar, Janice Kang, Tonatiuh Ocampo, Michael Evangelopoulos, Zhenyu Han, Sergej Kudruk, Jochen Lorch*, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)7629-7636
Number of pages8
JournalNano letters
Volume24
Issue number25
DOIs
StatePublished - Jun 26 2024

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

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