Nature communicationsMar 4, 2025

Using RNA in lipid particles to trigger COVID-19 immune responses for cancer treatment

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 12, 2026

Abstract

AA2 (LNP) encapsulating spike mRNA elicits stronger T-cell immunity than FDA-approved LNPs.

Lipid nanoparticle-mRNA vaccines can engage T-cell immunity against the SARS-CoV-2 spike protein.
AA2 LNP shows superior delivery efficiency by generating stronger T-cell responses compared to ALC-0315 and SM-102.
AA15V LNP effectively delivers self-amplifying RNAs that promote the presentation of spike epitopes in tumors.
Intratumoral treatment with AA15V LNP-sSE-SCTs suppresses tumor growth and improves survival in mouse models of melanoma and lymphoma.
AA15V LNP-sSE-SCTs demonstrate potential efficacy in ex vivo human glioblastoma and lung cancer samples.

Simplified

(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 (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.

Key numbers

69.0%

Increase in T-cell expression

Percentage of B16F10 cells expressing SE-SCTs by day 3 post-treatment.

27.8%

Tumor suppression

Percentage of OVA-H-2Kb live B16F10 cells within tumor tissues after treatment.

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Funding

Competing interests

Competing interests: Y.D. is a scientific advisor in Arbor Biotechnologies. Y.D. is a co-founder and holds equity in Immunanoengineering Therapeutics. D.J.I. and R.W. are scientific advisory board members and hold equity in Strand Therapeutics. The remaining authors declare no competing interests.

PubMed

Using RNA in lipid particles to trigger COVID-19 immune responses for cancer treatment

Abstract

Key numbers

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Competing interests

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Abstract

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Full Text

Funding

Competing interests

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