# mRNA vaccines transform personalized lung cancer treatment

**Authors:** Kaiqi Wei, Zitong Wan, Miaomiao Wen, Shaowei Xin, Yinxi Zhou, Jun Wei, Jianfei Zhu, Chengbin Tang, Yanlu Xiong, Tao Jiang, Jie Lei

PMC · DOI: 10.3389/fimmu.2025.1707654 · Frontiers in Immunology · 2026-02-12

## TL;DR

mRNA vaccines show promise for personalized lung cancer treatment by boosting immune responses and overcoming limitations of traditional therapies.

## Contribution

This review highlights the unique advantages of mRNA vaccines for lung cancer and proposes strategies for their personalized clinical application.

## Key findings

- mRNA vaccines can induce long-lasting immune memory and help prevent cancer recurrence.
- Compared to traditional vaccines, mRNA vaccines offer lower toxicity and better personalization.
- Current clinical trials are exploring the effectiveness of mRNA vaccines in lung cancer treatment.

## Abstract

Targeted therapy and immunotherapy represent major innovations in the treatment of lung cancer. However, in patients with driver gene-positive tumors, the emergence of acquired resistance to targeted drugs is inevitable. As for immunotherapy, its efficacy in early-stage lung cancer patients remains uncertain due to strong immune heterogeneity. In advanced and locally advanced patients, high tumor mutational burden leads to significant genomic instability and tumor progression, and resistance still inevitably develops even with standard chemotherapy combined with immunotherapy. Cancer vaccines, as an approach that activates the antitumor immune cycle from its origin, offer advantages such as the ability to target multiple antigens, minimal off-target effects, a wide therapeutic window, and low toxicity. Furthermore, such vaccines can induce long-lasting immune memory and possess a certain capacity to remodel the tumor immune microenvironment, which helps prevent cancer recurrence, demonstrating broad prospects in lung cancer treatment. Currently, various types of tumor vaccines (including those based on microorganisms, peptides, proteins, exosomes, and DNA) have been developed, yet they often face limitations in safety, insufficient personalization, and immature production pipelines. In contrast, messenger RNA (mRNA)-based vaccines offer distinct advantages, including the efficient generation of protective immune responses, relatively low side effects, and lower acquisition costs, making them a forefront option for novel lung cancer therapies. This review summarizes the current research status of lung cancer vaccines, clarifies the unique therapeutic advantages of mRNA vaccines compared to traditional vaccine modalities, and highlights existing challenges associated with mRNA vaccines. It also provides an overview of current clinical trials of mRNA vaccines for lung cancer and proposes rational design and clinical application strategies for personalized mRNA vaccines within the framework of precision oncology, based on evidence-based medicine.

## Linked entities

- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** EIF4G1 (eukaryotic translation initiation factor 4 gamma 1) [NCBI Gene 1981] {aka EIF-4G1, EIF4F, EIF4G, EIF4GI, P220, PARK18}, OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, CTAG1A (cancer/testis antigen 1A) [NCBI Gene 246100] {aka CT6.1, ESO1, LAGE-2, LAGE2A, NY-ESO-1}, CCL21 (C-C motif chemokine ligand 21) [NCBI Gene 6366] {aka 6Ckine, CKb9, ECL, SCYA21, SLC, TCA4}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CD70 (CD70 molecule) [NCBI Gene 970] {aka CD27-L, CD27L, CD27LG, LPFS3, TNFSF7, TNLG8A}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TLR8 (toll like receptor 8) [NCBI Gene 51311] {aka CD288, IMD98, TLR-8, hTLR8}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MAGEA3 (MAGE family member A3) [NCBI Gene 4102] {aka CT1.3, HIP8, HYPD, MAGE3}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, SMOC1 (SPARC related modular calcium binding 1) [NCBI Gene 64093] {aka OAS}, PRAME (PRAME nuclear receptor transcriptional regulator) [NCBI Gene 23532] {aka CT130, MAPE, OIP-4, OIP4}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939] {aka CDA02, EIF-2A, MST089, MSTP004, MSTP089}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, NUSAP1 (nucleolar and spindle associated protein 1) [NCBI Gene 51203] {aka ANKT, BM037, LNP, NUSAP, PRO0310p1, Q0310}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, EIF2AK2 (eukaryotic translation initiation factor 2 alpha kinase 2) [NCBI Gene 5610] {aka PKR, PPP1R83, PRKR}, EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977] {aka AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, PABPC1 (poly(A) binding protein cytoplasmic 1) [NCBI Gene 26986] {aka PAB1, PABP, PABP1, PABPC2, PABPL1}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, Rnf216 (ring finger protein 216) [NCBI Gene 108086] {aka 2810055G22Rik, F830018F18Rik, TRIAD3, UIP83, Ubce7ip1}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, CLDN6 (claudin 6) [NCBI Gene 9074], TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, CAP1 (cyclase associated actin cytoskeleton regulatory protein 1) [NCBI Gene 10487] {aka CAP, CAP1-PEN}
- **Diseases:** death (MESH:D003643), precancerous lesions (MESH:D011230), bone metastasis (MESH:D009362), APC (MESH:C535887), toxicity (MESH:D064420), weight loss (MESH:D015431), chills (MESH:D023341), COVID-19 (MESH:D000086382), infection (MESH:D007239), infectious disease (MESH:D003141), smallpox (MESH:D012899), asthenia (MESH:D001247), melanoma (MESH:D008545), inflammation (MESH:D007249), esophageal squamous cell carcinoma (MESH:D000077277), diabetes insipidus (MESH:D003919), Cancer (MESH:D009369), Lung Cancer (MESH:D008175), myocarditis (MESH:D009205), fatigue (MESH:D005221), NSCLC tumors (MESH:D002289), fever (MESH:D005334)
- **Chemicals:** Montanide ISA 51 (MESH:C477385), BI 1361849 (-), MAD (MESH:C110804), cemiplimab (MESH:C000627974), N1-methyl-pseudouridine (MESH:C013608), Keytruda (MESH:C582435), durvalumab (MESH:C000613593), Lipid (MESH:D008055), DS-8201 (MESH:C000614160), lipopeptide (MESH:D055666), poly(A) (MESH:D011061), mPLA (MESH:C048436), tremelimumab (MESH:C520704), nivolumab (MESH:D000077594), platinum (MESH:D010984), polymer (MESH:D011108), polyethylene glycol (MESH:D011092), water (MESH:D014867), phospholipids (MESH:D010743), cholesterol (MESH:D002784), ethanol (MESH:D000431), TSAs (MESH:C481298)
- **Species:** Homo sapiens (human, species) [taxon 9606], Adenoviridae (family) [taxon 10508], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Lyssavirus rabies (species) [taxon 11292]
- **Mutations:** G13D, G12V, G12C, T790M

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936860/full.md

## References

124 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936860/full.md

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Source: https://tomesphere.com/paper/PMC12936860