tetano
Editor, Senior Moderator
Nat Commun
. 2025 Mar 4;16(1):2198.
doi: 10.1038/s41467-025-57149-2. LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment
Yonger Xue[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Xucheng Hou[SUP] #[/SUP][SUP] 5 6 7 [/SUP], Yichen Zhong[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yuebao Zhang[SUP] #[/SUP][SUP] 1 8 [/SUP], Shi Du[SUP] 1 2 3 4 [/SUP], Diana D Kang[SUP] 1 2 3 4 [/SUP], Leiming Wang[SUP] 2 3 4 [/SUP], Chang Wang[SUP] 1 2 3 4 [/SUP], Haoyuan Li[SUP] 2 3 4 [/SUP], Siyu Wang[SUP] 2 3 4 [/SUP], Zhengwei Liu[SUP] 2 3 4 [/SUP], Meng Tian[SUP] 2 3 4 [/SUP], Kaiyuan Guo[SUP] 2 3 4 [/SUP], Dinglingge Cao[SUP] 2 3 4 [/SUP], Binbin Deng[SUP] 9 [/SUP], David W McComb[SUP] 9 10 [/SUP], Eric Purisic[SUP] 11 12 13 [/SUP], Jinye Dai[SUP] 11 12 13 [/SUP], Pauline Hamon[SUP] 3 4 14 [/SUP], Brian D Brown[SUP] 2 3 4 14 [/SUP], Nadejda M Tsankova[SUP] 13 14 15 [/SUP], Miriam Merad[SUP] 3 4 14 16 17 18 [/SUP], Darrell J Irvine[SUP] 19 20 21 22 23 [/SUP], Ron Weiss[SUP] 19 24 25 [/SUP], Yizhou Dong[SUP] 26 27 28 29 30 31 32 33 [/SUP]
Affiliations
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.
. 2025 Mar 4;16(1):2198.
doi: 10.1038/s41467-025-57149-2. LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment
Yonger Xue[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Xucheng Hou[SUP] #[/SUP][SUP] 5 6 7 [/SUP], Yichen Zhong[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yuebao Zhang[SUP] #[/SUP][SUP] 1 8 [/SUP], Shi Du[SUP] 1 2 3 4 [/SUP], Diana D Kang[SUP] 1 2 3 4 [/SUP], Leiming Wang[SUP] 2 3 4 [/SUP], Chang Wang[SUP] 1 2 3 4 [/SUP], Haoyuan Li[SUP] 2 3 4 [/SUP], Siyu Wang[SUP] 2 3 4 [/SUP], Zhengwei Liu[SUP] 2 3 4 [/SUP], Meng Tian[SUP] 2 3 4 [/SUP], Kaiyuan Guo[SUP] 2 3 4 [/SUP], Dinglingge Cao[SUP] 2 3 4 [/SUP], Binbin Deng[SUP] 9 [/SUP], David W McComb[SUP] 9 10 [/SUP], Eric Purisic[SUP] 11 12 13 [/SUP], Jinye Dai[SUP] 11 12 13 [/SUP], Pauline Hamon[SUP] 3 4 14 [/SUP], Brian D Brown[SUP] 2 3 4 14 [/SUP], Nadejda M Tsankova[SUP] 13 14 15 [/SUP], Miriam Merad[SUP] 3 4 14 16 17 18 [/SUP], Darrell J Irvine[SUP] 19 20 21 22 23 [/SUP], Ron Weiss[SUP] 19 24 25 [/SUP], Yizhou Dong[SUP] 26 27 28 29 30 31 32 33 [/SUP]
Affiliations
- PMID: 40038251
- PMCID: PMC11880362
- DOI: 10.1038/s41467-025-57149-2
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.