황정민 (Northwestern University)

한빛사논문

조회175

Northwestern University

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Nano Lett., Jun 14 2024, | https://doi.org/10.1021/acs.nanolett.4c01392 DNA Anchoring Strength Directly Correlates with Spherical Nucleic Acid-Based HPV E7 Cancer Vaccine Potency

Jeongmin Hwang ¹, Jasper Wilson Dittmar², Janice Kang¹, Tonatiuh Ocampo ³, Michael Evangelopoulos ², Zhenyu Han ¹, Sergej Kudruk¹, Jochen Lorch ⁴, Chad A Mirkin^1,2

¹Department of Chemistry and International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

²Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

³Department of Interdisciplinary Biological Sciences, Northwestern University, 2 Sheridan Road, Evanston, Illinois 60208, United States.

⁴Department of Medicine, Hematology/Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, United States.

J.H. and J.W.D. contributed equally to this work.

Corresponding Authors : Jochen Lorch, Chad A. Mirkin

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 (E7 _11-19) 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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-07-04)
연구진국외 연구진
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