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Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines

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Abstract

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+  T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.

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Abbreviations

AFM:

Atomic force microscopy

BMDCs:

Bone marrow-derived dendritic cells

CpG:

Cytosine–phosphate–guanine

CpG ODN:

Cytidine–phosphate–guanosine oligonucleotide

CTLs:

Cytotoxic T lymphocytes

DCs:

Dendritic cells

DLS:

Dynamic light scattering

DMEM:

Dulbecco’s modified Eagle’s medium

ELISA:

Enzyme-linked immunosorbent assay

ELISPOT:

IFN-γ enzyme-linked immunospot

FBS:

Fetal bovine serum

LNs:

Lymph nodes

MHC-I:

Major histocompatibility complex class I

NitraTh:

Nitrated T helper cell epitope

PBMCs:

Peripheral blood mononuclear cells

PBS:

Phosphate-buffered saline

Poly-ICLC:

Polyinosinic–polycytidylic acid

SLPs:

Synthetic long peptides

TEM:

Transmission electron microscopy

TILs:

Tumor-infiltrating lymphocytes

TLR9:

Toll-like receptor 9

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 82073754, No. 81973222, No. 82273840), the Key R & D Program of Xinjiang Uygur Autonomous Region (2020B03003), and the “Double First-Class” University Project (No. CPU2018GF08).

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Author notes

  1. Yanliang Kang and Wanli Zhang have contributed equally to this study.

Authors and Affiliations

  1. Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China

    Yanliang Kang, Wanli Zhang, Qiumin Yu, Le Gao, Jiale Quan, Fangling Gu, Yuxin Wu, Yahong Tian, Zijie Wu, Shishuai Shao, Hongyou Zhou, Shukang Duan, Yixiang Zhou, Xiangdong Gao, Hong Tian & Wenbing Yao

  2. Department of General Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China

    Li Zhang

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Contributions

YK and WZ contributed equally to this study. YK and HT designed the project, conducted data analyses. HT, YK and WZ wrote the manuscript. WZ, QY, LG, JQ, FG, XW, YT, ZW, SS, HZ, and YZ were involved in the animal studies. LZ, XG, HT, and WY conceived the study.

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Correspondence to Li Zhang, Xiangdong Gao, Hong Tian or Wenbing Yao.

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Kang, Y., Zhang, W., Yu, Q. et al. Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines. Cancer Immunol Immunother 72, 2741–2755 (2023). https://doi.org/10.1007/s00262-023-03446-y

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