Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy

Meiyi XIN; Yuhong LIN; Kai ZHAO

doi:10.19401/j.cnki.1007-3639.2024.05.008

您当前的位置：

首页 >

文章列表页 >

Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy

Review | 更新时间：2025-12-31

- Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy
- China Oncology Vol. 34, Issue 5, Pages: 509-516(2024)
- 作者机构：
  
  1. 黑龙江大学生命科学学院，农业微生物技术教育部工程研究中心，黑龙江省寒区植物基因与生物发酵重点实验室，黑龙江哈尔滨 150080
  2. 台州学院生命科学学院，浙江省植物进化生态学与保护重点实验室，台州市生物医药与高端剂型重点实验室，浙江台州 318000
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.05.008
  CLC： R730.51
- Received：04 March 2024，
  
  Revised：2024-04-03，
  
  Published：30 May 2024
- 稿件说明：
移动端阅览
Meiyi XIN, Yuhong LIN, Kai ZHAO. Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy[J]. China Oncology, 2024, 34(5): 509-516.
DOI：

Meiyi XIN, Yuhong LIN, Kai ZHAO. Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy[J]. China Oncology, 2024, 34(5): 509-516. DOI： 10.19401/j.cnki.1007-3639.2024.05.008.

摘要

由于传统抗肿瘤手段在临床应用中具有特异度低、不良反应大的缺点，新型的抗肿瘤免疫疗法受到关注并逐渐得以应用。肿瘤免疫疗法通过调节机体免疫系统，增强抗肿瘤免疫应答以实现对肿瘤的控制和杀伤。肿瘤免疫疗法包括免疫检查点阻断疗法、过继细胞免疫治疗和肿瘤疫苗。其中，肿瘤疫苗通过递送肿瘤细胞特异性抗原刺激免疫系统产生特异性免疫细胞或抗体从而消除肿瘤细胞以达到治疗肿瘤的目的。近年来，mRNA疫苗相关领域迅速发展，所需的mRNA在合成及制备方面的工艺日趋成熟，为肿瘤mRNA疫苗的研究奠定了良好的基础。因mRNA具有易被降解、无法自主进入细胞等特点，此类疫苗需要合适的递送载体才能成功地被细胞摄取并发挥功效。因此，mRNA疫苗递送系统的发展成为其能否被更好地利用的关键，这也是在肿瘤治疗领域里mRNA疫苗能否被开发利用至临床阶段的重要一环。本文简要介绍肿瘤的免疫治疗方法、肿瘤疫苗种类和肿瘤mRNA疫苗的作用机制及制备方法，介绍用于肿瘤治疗的免疫疗法中mRNA疫苗及其常见的递送系统的研究进展和相关应用，并对进入临床试验阶段的肿瘤mRNA疫苗进行归纳和整理，以期为今后针对肿瘤的mRNA疫苗的研究工作提供帮助。

Abstract

Due to the drawbacks of low specificity and high risk of side effects of traditional anti-tumor treatments in clinical practice

novel anti-tumor immunotherapy has received attention and has been gradually applied. Tumor immunotherapy is to enhance the anti-tumor immune response by regulating the body’s immune system in order to achieve control and killing of tumors. Tumor immunotherapies include immune checkpoint blockade therapy

over-the-counter cellular immunotherapy and tumor vaccines. Among them

the tumor vaccine stimulates the immune system to produce specific immune cells or antibodies by delivering tumor cell-specific antigens thereby eliminating the tumor cells for the purpose of treating the tumor. In recent years

The field of mRNA vaccines is developing rapidly

and the required mRNA in the synthesis and preparation of the process has been developed and matured

laying a good foundation for the research of tumor mRNA vaccine. Because of the fact that mRNA is easily degraded and cannot enter the cell autonomously

this vaccine requires a suitable delivery vehicle to be successfully taken up by the cell to be effective. Therefore

the development of mRNA vaccine delivery systems has become critical for their better utilization

which is also an important part of whether mRNA vaccines can be developed and utilized for the clinical stage in the field of tumor therapy. This paper briefly introduced the immunotherapeutic methods for tumors

types of tumor vaccines and the mechanism of action and preparation methods of tumor mRNA vaccines

reviewed the research progress and related applications of mRNA vaccines and their common delivery systems in immunotherapy for tumor treatment

and summarized the tumor mRNA vaccines that entered into the phase of clinical trials with the aim of providing assistance for the research of mRNA vaccines for tumors in the future.

关键词

Keywords

references

LIU Y X , YAN Q J , ZENG Z Y , et al. Advances and prospects of mRNA vaccines in cancer immunotherapy [J ] . Biochim Biophys Acta Rev Cancer , 2024 , 1879 ( 2 ): 189068.

ZHANG A , JI Q M , SHENG X , et al. mRNA vaccine in gastrointestinal tumors: immunomodulatory effects and immunotherapy [J ] . Biomedecine Pharmacother , 2023 , 166 : 115361 .

WOLCHOK J . Putting the immunologic brakes on cancer [J ] . Cell , 2018 , 175 ( 6 ): 1452 - 1454 . DOI: S0092-8674(18)31465-X http://doi.org/S0092-8674(18)31465-X

SHI S J , HUANG J C , KUANG Y , et al. Stability and Hopf bifurcation of a tumor-immune system interaction model with an immune checkpoint inhibitor [J ] . Commun Nonlinear Sci Numer Simul , 2023 , 118 : 106996 .

ZHU C J , WU Q , SHENG T , et al. Rationally designed approaches to augment CAR-T therapy for solid tumor treatment [J ] . Bioact Mater , 2024 , 33 : 377 - 395 . DOI: 10.1016/j.bioactmat.2023.11.002 http://doi.org/10.1016/j.bioactmat.2023.11.002

LIU C P , WANG Y C , LI L M , et al. Engineered extracellular vesicles and their mimetics for cancer immunotherapy [J ] . J Control Release , 2022 , 349 : 679 - 698 .

LIU J , FU M Y , WANG M N , et al. Cancer vaccines as promising immuno-therapeutics: platforms and current progress [J ] . J Hematol Oncol , 2022 , 15 ( 1 ): 28.

GUO C Q , MANJILI M H , SUBJECK J R , et al. Therapeutic cancer vaccines: past, present, and future [J ] . Adv Cancer Res , 2013 , 119 : 421 - 475 . DOI: 10.1016/B978-0-12-407190-2.00007-1 http://doi.org/10.1016/B978-0-12-407190-2.00007-1

TÜRECI Ö , VORMEHR M , DIKEN M , et al. Targeting the heterogeneity of cancer with individualized neoepitope vaccines [J ] . Clin Cancer Res , 2016 , 22 ( 8 ): 1885 - 1896 . DOI: 10.1158/1078-0432.CCR-15-1509 http://doi.org/10.1158/1078-0432.CCR-15-1509

QIN X Y , YANG T , XU H B , et al. Dying tumor cells-inspired vaccine for boosting humoral and cellular immunity against cancer [J ] . J Control Release , 2023 , 359 : 359 - 372 .

GEBRE M S , BRITO L A , TOSTANOSKI L H , et al. Novel approaches for vaccine development [J ] . Cell , 2021 , 184 ( 6 ): 1589 - 1603 . DOI: 10.1016/j.cell.2021.02.030 http://doi.org/10.1016/j.cell.2021.02.030

ZHANG X Y , CUI H Q , ZHANG W J , et al. Engineered tumor cell-derived vaccines against cancer: the art of combating poison with poison [J ] . Bioact Mater , 2023 , 22 : 491 - 517 . DOI: 10.1016/j.bioactmat.2022.10.016 http://doi.org/10.1016/j.bioactmat.2022.10.016

PARDI N , HOGAN M J , PORTER F W , et al. mRNA vaccines-a new era in vaccinology [J ] . Nat Rev Drug Discov , 2018 , 17 ( 4 ): 261 - 279 .

WANG Y , ZHANG Z Q , LUO J W , et al. mRNA vaccine: a potential therapeutic strategy [J ] . Mol Cancer , 2021 , 20 ( 1 ): 33.

STEINER P A , CORTE D D , GEIJO J , et al. Highly variable mRNA half-life time within marine bacterial taxa and functional genes [J ] . Environ Microbiol , 2019 , 21 ( 10 ): 3873 - 3884 . DOI: 10.1111/1462-2920.14737 http://doi.org/10.1111/1462-2920.14737

YEAPURI P , OLSON K E , LU Y M , et al. Development of an extended half-life GM-CSF fusion protein for Parkinson’s disease [J ] . J Control Release , 2022 , 348 : 951 - 965 .

YAN Y , LIU X Y , LU A , et al. Non-viral vectors for RNA delivery [J ] . J Control Release , 2022 , 342 : 241 - 279 .

CHU Y Y , ZHANG Y , WANG Q K , et al. A transformer-based model to predict peptide-HLA class Ⅰ binding and optimize mutated peptides for vaccine design [J ] . Nat Mach Intell , 2022 , 4 : 300 - 311 .

BELL M R , KUTZLER M A . An old problem with new solutions: strategies to improve vaccine efficacy in the elderly [J ] . Adv Drug Deliv Rev , 2022 , 183 : 114175 .

XU S Q , YANG K P , LI R , et al. mRNA vaccine era-mechanisms, drug platform and clinical prospection [J ] . Int J Mol Sci , 2020 , 21 ( 18 ): 6582.

CHEN G , ZHAO B W , RUIZ E F , et al. Advances in the polymeric delivery of nucleic acid vaccines [J ] . Theranostics , 2022 , 12 ( 9 ): 4081 - 4109 . DOI: 10.7150/thno.70853 http://doi.org/10.7150/thno.70853

WEBER J S , CARLINO M S , KHATTAK A , et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study [J ] . Lancet , 2024 , 403 ( 10427 ): 632 - 644 .

SUNG H , FERLAY J , SIEGEL R L , et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .

ROJAS L A , SETHNA Z , SOARES K C , et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer [J ] . Nature , 2023 , 618 ( 7963 ): 144 - 150 .

LIANG X P , LI D P , LENG S L , et al. RNA-based pharmacotherapy for tumors: from bench to clinic and back [J ] . Biomedecine Pharmacother , 2020 , 125 : 109997 .

MITCHELL W . The 1986 Nobel Prize in chemistry [J ] . Science , 1986 , 234 ( 4777 ): 673 - 674 .

SCHMITT W E , STASSAR M J , SCHMITT W , et al. In vitro induction of a bladder cancer-specific T-cell response by mRNA-transfected dendritic cells [J ] . J Cancer Res Clin Oncol , 2001 , 127 ( 3 ): 203 - 206 .

MA S J , LI X L , MAI Y P , et al. Immunotherapeutic treatment of lung cancer and bone metastasis with a mPLA/mRNA tumor vaccine [J ] . Acta Biomater , 2023 , 169 : 489 - 499 . DOI: 10.1016/j.actbio.2023.07.059 http://doi.org/10.1016/j.actbio.2023.07.059

BERNARD M C , BAZIN E , PETIOT N , et al. The impact of nucleoside base modification in mRNA vaccine is influenced by the chemistry of its lipid nanoparticle delivery system [J ] . Mol Ther Nucleic Acids , 2023 , 32 : 794 - 806 .

MEULEWAETER S , ZHANG Y , WADHWA A , et al. Considerations on the design of lipid-based mRNA vaccines against cancer [J ] . J Mol Biol , 2024 , 436 ( 2 ): 168385.

YAN Y F , LIU X M , WANG L Y , et al. Branched hydrophobic tails in lipid nanoparticles enhance mRNA delivery for cancer immunotherapy [J ] . Biomaterials , 2023 , 301 : 122279 .

SUN B , WU W X , NARASIPURA E A , et al. Engineering nanoparticle toolkits for mRNA delivery [J ] . Adv Drug Deliv Rev , 2023 , 200 : 115042 .

QU Y , XU J , ZHANG T , et al. Advanced nano-based strategies for mRNA tumor vaccine [J ] . Acta Pharm Sin B , 2024 , 14 ( 1 ): 170 - 189 .

ESTAPÉ SENTI M , GARCÍA DEL VALLE L , SCHIFFELERS R M . mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond [J ] . Adv Drug Deliv Rev , 2024 , 206 : 115190 .

DIMITRIADIS G J . Translation of rabbit globin mRNA introduced by liposomes into mouse lymphocytes [J ] . Nature , 1978 , 274 ( 5674 ): 923 - 924 .

CHEN Z , MENG C Y , MAI J H , et al. An mRNA vaccine elicits STING-dependent antitumor immune responses [J ] . Acta Pharm Sin B , 2023 , 13 ( 3 ): 1274 - 1286 . DOI: 10.1016/j.apsb.2022.11.013 http://doi.org/10.1016/j.apsb.2022.11.013

SHARMA P , HOORN D , AITHA A , et al. The immunostimulatory nature of mRNA lipid nanoparticles [J ] . Adv Drug Deliv Rev , 2024 , 205 : 115175 .

PARMAR M B , K C R B , LÖBENBERG R , et al. Additive polyplexes to undertake siRNA therapy against CDC20 and survivin in breast cancer cells [J ] . Biomacromolecules , 2018 , 19 ( 11 ): 4193 - 4206 . DOI: 10.1021/acs.biomac.8b00918 http://doi.org/10.1021/acs.biomac.8b00918

PERCHE F , BENVEGNU T , BERCHEL M , et al. Enhancement of dendritic cells transfection in vivo and of vaccination against B16F10 melanoma with mannosylated histidylated lipopolyplexes loaded with tumor antigen messenger RNA [J ] . Nanomed-Nanotechnol Biol Med , 2011 , 7 ( 4 ): 445 - 453 .

ARYA S , LIN Q B , ZHOU N , et al. Strong immune responses induced by direct local injections of modified mRNA-lipid nano complexes [J ] . Mol Ther Nucleic Acids , 2020 , 19 : 1098 - 1109 .

YANG A F , BAI Y , DONG X , et al. Hydrogel/nanoadjuvant-mediated combined cell vaccines for cancer immunotherapy [J ] . Acta Biomater , 2021 , 133 : 257 - 267 . DOI: 10.1016/j.actbio.2021.08.014 http://doi.org/10.1016/j.actbio.2021.08.014

SHI S X , YANG K , HONG H , et al. VEGFR targeting leads to significantly enhanced tumor uptake of nanographene oxide invivo [J ] . Biomaterials , 2015 , 39 : 39 - 46 .

MALLA R , SRILATHA M , FARRAN B , et al. mRNA vaccines and their delivery strategies: a journey from infectious diseases to cancer [J ] . Mol Ther , 2024 , 32 ( 1 ): 13 - 31 .

CHARBE N B , AMNERKAR N D , RAMESH B , et al. Small interfering RNA for cancer treatment: overcoming hurdles in delivery [J ] . Acta Pharm Sin B , 2020 , 10 ( 11 ): 2075 - 2109 . DOI: 10.1016/j.apsb.2020.10.005 http://doi.org/10.1016/j.apsb.2020.10.005

YIHUNIE W , NIBRET G , ASCHALE Y . Recent advances in messenger ribonucleic acid (mRNA) vaccines and their delivery systems: a review [J ] . Clin Pharmacol , 2023 , 15 : 77 - 98 .

DEMIR-DORA D , ÖNER F . Development and evaluation of polyethylenimine polyplexes as non-viral vectors for delivery of plasmid DNA encoding shRNA against STAT3 activity into triple negative breast cancer cells [J ] . J Drug Deliv Sci Technol , 2023 , 82 : 104113 .

WANG K L , WANG X Y , JIANG D , et al. Delivery of mRNA vaccines and anti-PDL1 siRNA through non-invasive transcutaneous route effectively inhibits tumor growth [J ] . Compos Part B Eng , 2022 , 233 : 109648 .

ZHANG Z H , QIAN Y , JIN H L , et al. Peptide-lipid nano-delivery system for cancer theranostics [J ] . Nanomed Nanotechnol Biol Med , 2018 , 14 ( 5 ): 1867.

KORDALIVAND N , TONDINI E , LAU C Y J , et al. Cationic synthetic long peptides-loaded nanogels: an efficient therapeutic vaccine formulation for induction of T-cell responses [J ] . J Control Release , 2019 , 315 : 114 - 125 .

LOU B , KOKER S D , LAU C Y J , et al. mRNA polyplexes with post-conjugated GALA peptides efficiently target, transfect, and activate antigen presenting cells [J ] . Bioconjug Chem , 2019 , 30 ( 2 ): 461 - 475 .

MAI Y P , GUO J S , ZHAO Y , et al. Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity [J ] . Cell Immunol , 2020 , 354 : 104143 .

LIN H X , ZHOU R H , YU T J , et al. An acid-targeting peptide can be used as a carrier for photodynamic therapy (PDT) [J ] . Mater Today Commun , 2022 , 31 : 103659 .

CHEN S , LI J G , MA X Y , et al. Cationic peptide-modified gold nanostars as efficient delivery platform for RNA interference antitumor therapy [J ] . Polymers , 2021 , 13 ( 21 ): 3764.

SUNG J , ALGHOUL Z , LONG D P , et al. Oral delivery of IL-22 mRNA-loaded lipid nanoparticles targeting the injured intestinal mucosa: a novel therapeutic solution to treat ulcerative colitis [J ] . Biomaterials , 2022 , 288 : 121707 .

KITAGAWA K , TATSUMI M , KATO M , et al. An oral cancer vaccine using a Bifidobacterium vector suppresses tumor growth in a syngeneic mouse bladder cancer model [J ] . Mol Ther Oncolytics , 2021 , 22 : 592 - 603 .

UCHIDA S , KINOH H , ISHII T , et al. Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety [J ] . Biomaterials , 2016 , 82 : 221 - 228 . DOI: 10.1016/j.biomaterials.2015.12.031 http://doi.org/10.1016/j.biomaterials.2015.12.031

CHENG C , CONVERTINE A J , STAYTON P S , et al. Multifunctional triblock copolymers for intracellular messenger RNA delivery [J ] . Biomaterials , 2012 , 33 ( 28 ): 6868 - 6876 . DOI: 10.1016/j.biomaterials.2012.06.020 http://doi.org/10.1016/j.biomaterials.2012.06.020

LIU Y H , LI S H , LIN S Y , et al. A tetrahedral framework nucleic acid based multifunctional nanocapsule for tumor prophylactic mRNA vaccination [J ] . Chin Chemical Lett , 2023 , 34 ( 7 ): 107987.

YAO R H , XIE C Y , XIA X J . Recent progress in mRNA cancer vaccines [J ] . Hum Vaccin Immunother , 2024 , 20 ( 1 ): 2307187.

HE Q , GAO H , TAN D J , et al. mRNA cancer vaccines: advances, trends and challenges [J ] . Acta Pharm Sin B , 2022 , 12 ( 7 ): 2969 - 2989 .

CHUNG D J , SHARMA S , RANGESA M , et al. Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after auto-transplant [J ] . Blood Adv , 2022 , 6 ( 5 ): 1547 - 1558 .

FIGDOR C G , De VRIES I J , LESTERHUIS W J , et al. Dendritic cell immunotherapy: mapping the way [J ] . Nat Med , 10 ( 5 ): 475 - 80 .

LESTERHUIS W J , AARNTZEN E H , DE VRIES I J , et al. Dendritic cell vaccines in melanoma: from promise to proof? [J ] . Crit Rev Oncol Hematol , 2008 , 66 ( 2 ): 118 - 134 .

De VRIES I J , BERNSEN M R , LESTERHUIS W J , et al. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome [J ] . J Clin Oncol , 2005 , 23 ( 24 ): 5779 - 5787 . DOI: 10.1200/JCO.2005.06.478 http://doi.org/10.1200/JCO.2005.06.478

Views

1780

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Targeted therapy and immunotherapy combined with chemotherapy bring effective response to AFP positive colon cancer patients: a case report and literature review

Mechanism study of MYC promoting proliferation and metastasis in prostate cancer by targeting CD47

MDT consensus on immunotherapy for locally advanced head and neck squamous cell carcinoma (2025 edition)

Research status and progress of third-line treatment for metastatic colorectal cancer

The ten-year evolution of systemic therapy for advanced differentiated thyroid cancer: a comparison between the 2015 and 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer

Related Author

LIU Miao

LI Jinze

WU Chensi

ZHANG Fengbin

GAO Hongsheng

ZHANG Ruixing

Hao LIU

Junjie SU

Related Institution

Department of Pathology, the Fourth Hospital of Hebei Medical University

Department of Gastroenterology, the Fourth Hospital of Hebei Medical University

Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology

College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology

Committee of Head and Neck Cancer, Chinese Society of Clinical Oncology

AI问答

⁰