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LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment

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  • Yonger Xue

    (The Ohio State University
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Xucheng Hou

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Yichen Zhong

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Yuebao Zhang

    (The Ohio State University
    Chongqing Medical University)

  • Shi Du

    (The Ohio State University
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Diana D. Kang

    (The Ohio State University
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Leiming Wang

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Chang Wang

    (The Ohio State University
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Haoyuan Li

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Siyu Wang

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Zhengwei Liu

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Meng Tian

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Kaiyuan Guo

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Dinglingge Cao

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Binbin Deng

    (The Ohio State University)

  • David W. McComb

    (The Ohio State University
    The Ohio State University)

  • Eric Purisic

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Jinye Dai

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Pauline Hamon

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Brian D. Brown

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Nadejda M. Tsankova

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Miriam Merad

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Darrell J. Irvine

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Ron Weiss

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Yizhou Dong

    (The Ohio State University
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

Lipid nanoparticle (LNP)-mRNA vaccines have demonstrated protective capability in combating SARS-CoV-2. Their extensive deployment across the global population leads to the broad presence of T-cell immunity against the SARS-CoV-2 spike protein, presenting an opportunity to harness this immunological response as a universal antigen target for cancer treatment. Herein, we design and synthesize a series of amino alcohol- or amino acid-derived ionizable lipids (AA lipids) and develop an LNP-RNA-based antigen presentation platform to redirect spike-specific T-cell immunity against cancer in mouse models. First, in a prime-boost regimen, AA2 LNP encapsulating spike mRNA elicit stronger T-cell immunity against the spike epitopes compared to FDA-approved LNPs (ALC-0315 and SM-102), highlighting the superior delivery efficiency of AA2 LNP. Next, AA15V LNP efficiently delivers self-amplifying RNAs (saRNAs) encoding spike epitope-loaded single-chain trimer (sSE-SCT) MHC I molecules into tumor tissues, thereby inducing the presentation of spike epitopes. Our results show that a single intratumoral (i.t.) treatment of AA15V LNP-sSE-SCTs suppresses tumor growth and extends the survival of B16F10 melanoma and A20 lymphoma tumor-bearing mice vaccinated with AA2 LNP-spike mRNA. Additionally, AA15V LNP-sSE-SCTs enable SE-SCT expression in ex vivo human glioblastoma and lung cancer samples, suggesting its potential in clinical translation.

Suggested Citation

  • Yonger Xue & Xucheng Hou & Yichen Zhong & Yuebao Zhang & Shi Du & Diana D. Kang & Leiming Wang & Chang Wang & Haoyuan Li & Siyu Wang & Zhengwei Liu & Meng Tian & Kaiyuan Guo & Dinglingge Cao & Binbin , 2025. "LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57149-2
    DOI: 10.1038/s41467-025-57149-2
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    References listed on IDEAS

    as
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