LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment
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 immu...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57149-2 |
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| author | 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 Deng David W. McComb Eric Purisic Jinye Dai Pauline Hamon Brian D. Brown Nadejda M. Tsankova Miriam Merad Darrell J. Irvine Ron Weiss Yizhou Dong |
| author_facet | 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 Deng David W. McComb Eric Purisic Jinye Dai Pauline Hamon Brian D. Brown Nadejda M. Tsankova Miriam Merad Darrell J. Irvine Ron Weiss Yizhou Dong |
| author_sort | Yonger Xue |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eb3d9c9048b94ce3af2377a15c82def4 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-eb3d9c9048b94ce3af2377a15c82def42025-08-20T01:57:25ZengNature PortfolioNature Communications2041-17232025-03-0116111310.1038/s41467-025-57149-2LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatmentYonger Xue0Xucheng Hou1Yichen Zhong2Yuebao Zhang3Shi Du4Diana D. Kang5Leiming Wang6Chang Wang7Haoyuan Li8Siyu Wang9Zhengwei Liu10Meng Tian11Kaiyuan Guo12Dinglingge Cao13Binbin Deng14David W. McComb15Eric Purisic16Jinye Dai17Pauline Hamon18Brian D. Brown19Nadejda M. Tsankova20Miriam Merad21Darrell J. Irvine22Ron Weiss23Yizhou Dong24Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiCenter for Electron Microscopy and Analysis, The Ohio State UniversityCenter for Electron Microscopy and Analysis, The Ohio State UniversityDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiMarc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount SinaiIcahn Genomics Institute, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, Icahn School of Medicine at Mount SinaiMarc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount SinaiDepartment of Biological Engineering, Massachusetts Institute of TechnologyDepartment of Biological Engineering, Massachusetts Institute of TechnologyDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State UniversityAbstract 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.https://doi.org/10.1038/s41467-025-57149-2 |
| spellingShingle | 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 Deng David W. McComb Eric Purisic Jinye Dai Pauline Hamon Brian D. Brown Nadejda M. Tsankova Miriam Merad Darrell J. Irvine Ron Weiss Yizhou Dong LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment Nature Communications |
| title | LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment |
| title_full | LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment |
| title_fullStr | LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment |
| title_full_unstemmed | LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment |
| title_short | LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment |
| title_sort | lnp rna mediated antigen presentation leverages sars cov 2 specific immunity for cancer treatment |
| url | https://doi.org/10.1038/s41467-025-57149-2 |
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