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Curated Papers > Recent high-impact research on "mRNA vaccines" (IF ≥ 30, last 5 years)

mRNA vaccine for cancer immunotherapy. ​

Literature Information ​

DOI10.1186/s12943-021-01335-5
PMID33632261
JournalMolecular cancer
Impact Factor33.9
JCR QuartileQ1
Publication Year2021
Times Cited419
KeywordsCancer immunotherapy, Cancer vaccine, Ionizable lipids, Lipid nanoparticles (LNPs), Personalized vaccine
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Review
ISSN1476-4598
Pages41
Issue20(1)
AuthorsLei Miao, Yu Zhang, Leaf Huang

TL;DR ​

This review highlights the potential of mRNA vaccines as a powerful platform for cancer immunotherapy, emphasizing their ability to efficiently express tumor antigens and stimulate immune responses. Despite challenges like instability and delivery efficiency, advancements in mRNA modifications and formulation methods, along with recent FDA approvals for COVID-19 vaccines, suggest a promising future for mRNA cancer vaccines in enhancing anti-tumor immunity and improving treatment outcomes.

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Cancer immunotherapy · Cancer vaccine · Ionizable lipids · Lipid nanoparticles (LNPs) · Personalized vaccine

Abstract ​

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

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Primary Questions Addressed ​

  1. What are the specific modifications to mRNA structures that have shown promise in enhancing the stability and delivery of cancer vaccines?
  2. How do the immune responses generated by mRNA vaccines compare to those elicited by traditional cancer immunotherapies?
  3. What role do lipid nanoparticles play in the effectiveness of mRNA vaccines for cancer treatment?
  4. Can the co-delivery of mRNA vaccines with checkpoint inhibitors lead to synergistic effects in cancer therapy, and what evidence supports this?
  5. What challenges remain in the clinical application of mRNA vaccines for various types of cancers, and how are researchers addressing these issues?

Key Findings ​

Research Background and Objectives ​

mRNA vaccines have emerged as a promising platform for cancer immunotherapy due to their ability to efficiently express tumor antigens, activate antigen-presenting cells (APCs), and stimulate both innate and adaptive immune responses. This review discusses the advancements and challenges associated with mRNA cancer vaccines, exploring their potential applications and future directions in cancer treatment.

Main Methods/Materials/Experimental Design ​

The review highlights various strategies employed to enhance the efficacy of mRNA vaccines, including:

  • mRNA Modifications: Codon optimization, nucleotide modifications, and self-amplifying mRNAs (SAMs) to improve stability and translation efficiency.
  • Delivery Systems: Formulations using lipid nanoparticles (LNPs), polymers, and peptides to facilitate efficient mRNA delivery to APCs.
  • Combination Therapies: Co-delivery of mRNA vaccines with other immunotherapeutic agents, such as checkpoint inhibitors, to enhance anti-tumor immunity.
Mermaid diagram

Key Results and Findings ​

  • Efficacy of mRNA Vaccines: Over twenty mRNA-based immunotherapies have entered clinical trials, showing promising results in treating solid tumors.
  • Technological Innovations: Advances in mRNA technology have improved stability and translation efficiency, while LNPs have been particularly effective in enhancing delivery.
  • Clinical Outcomes: Recent clinical trials have demonstrated the safety and efficacy of mRNA vaccines, with some achieving FDA approval for COVID-19, thereby increasing interest in their application for cancer.

Main Conclusions/Significance/Innovation ​

mRNA vaccines represent a versatile and powerful tool for cancer immunotherapy. Their ability to encode multiple antigens and induce robust immune responses positions them as a leading candidate for personalized cancer vaccines. The review emphasizes the need for continued innovation in mRNA technology and delivery systems to overcome existing challenges, particularly in the context of diverse tumor antigens and immune evasion.

Research Limitations and Future Directions ​

  • Challenges in Antigen Identification: The variability of tumor antigens poses a significant hurdle for effective vaccine development.
  • Innate Immunity Activation: The inherent immunogenicity of mRNA can lead to systemic inflammation, necessitating careful design to mitigate adverse effects.
  • Future Research: There is a strong focus on the development of personalized neoantigen vaccines, leveraging advancements in sequencing and bioinformatics to tailor treatments to individual patients.

Overall, mRNA vaccines hold great promise for the future of cancer immunotherapy, with ongoing research aimed at refining their design and application to maximize therapeutic efficacy.

References ​

  1. Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive®) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer. - Martin Sebastian;Alexandros Papachristofilou;Christian Weiss;Martin Früh;Richard Cathomas;Wolfgang Hilbe;Thomas Wehler;Gerd Rippin;Sven D Koch;Birgit Scheel;Mariola Fotin-Mleczek;Regina Heidenreich;Karl-Josef Kallen;Ulrike Gnad-Vogt;Alfred Zippelius - BMC cancer (2014)
  2. Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In Vivo Genome Editing of Multiple Therapeutic Gene Targets. - Anthony Conway;Matthew Mendel;Kenneth Kim;Kyle McGovern;Alisa Boyko;Lei Zhang;Jeffrey C Miller;Russell C DeKelver;David E Paschon;Barbara L Mui;Paulo J C Lin;Ying K Tam;Chris Barbosa;Tom Redelmeier;Michael C Holmes;Gary Lee - Molecular therapy : the journal of the American Society of Gene Therapy (2019)
  3. Systemic delivery of factor IX messenger RNA for protein replacement therapy. - Suvasini Ramaswamy;Nina Tonnu;Kiyoshi Tachikawa;Pattraranee Limphong;Jerel B Vega;Priya P Karmali;Pad Chivukula;Inder M Verma - Proceedings of the National Academy of Sciences of the United States of America (2017)
  4. A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases. - Yanina Jansen;Vibeke Kruse;Jurgen Corthals;Kelly Schats;Pieter-Jan van Dam;Teofila Seremet;Carlo Heirman;Lieve Brochez;Mark Kockx;Kris Thielemans;Bart Neyns - Cancer immunology, immunotherapy : CII (2020)
  5. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. - Katalin Karikó;Michael Buckstein;Houping Ni;Drew Weissman - Immunity (2005)
  6. Overcoming HLA restriction in clinical trials: Immune monitoring of mRNA-loaded DC therapy. - An M T Van Nuffel;Sofie Wilgenhof;Kris Thielemans;Aude Bonehill - Oncoimmunology (2012)
  7. Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs. - Parimal Kumar;Trevor R Sweeney;Maxim A Skabkin;Olga V Skabkina;Christopher U T Hellen;Tatyana V Pestova - Nucleic acids research (2014)
  8. Self-Replicating RNA Viruses for RNA Therapeutics. - Kenneth Lundstrom - Molecules (Basel, Switzerland) (2018)
  9. An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo. - Bin Li;Xiao Luo;Binbin Deng;Junfeng Wang;David W McComb;Yimin Shi;Karin M L Gaensler;Xu Tan;Amy L Dunn;Bryce A Kerlin;Yizhou Dong - Nano letters (2015)
  10. Cap-dependent translation initiation factor, eIF4E, is the target for Ouabain-mediated inhibition of HIF-1α. - Ji Cao;Lingjuan He;Guanyu Lin;Chunqi Hu;Rong Dong;Jun Zhang;Hong Zhu;Yongzhou Hu;Carston R Wagner;Qiaojun He;Bo Yang - Biochemical pharmacology (2014)

Literatures Citing This Work ​

  1. Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. - Dinah V Parums - Medical science monitor : international medical journal of experimental and clinical research (2021)
  2. Minicircles for a two-step blood biomarker and PET imaging early cancer detection strategy. - Elise R Robinson;Gayatri Gowrishankar;Aloma L D'Souza;Azadeh Kheirolomoom;Tom Haywood;Sharon S Hori;Hui-Yen Chuang;Yitian Zeng;Spencer K Tumbale;Amin Aalipour;Corinne Beinat;Israt S Alam;Ataya Sathirachinda;Masamitsu Kanada;Ramasamy Paulmurugan;Katherine W Ferrara;Sanjiv S Gambhir - Journal of controlled release : official journal of the Controlled Release Society (2021)
  3. Scrutinizing Coronaviruses Using Publicly Available Bioinformatic Tools: The Viral Structural Proteins as a Case Study. - Sonia Beeckmans;Edilbert Van Driessche - Frontiers in molecular biosciences (2021)
  4. Virus-inspired strategies for cancer therapy. - Xiao Yin Ma;Brett D Hill;Trang Hoang;Fei Wen - Seminars in cancer biology (2022)
  5. Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines. - Alexander J Stephens;Nicola A Burgess-Brown;Shisong Jiang - Frontiers in immunology (2021)
  6. Tumor RNA-loaded nanoliposomes increases the anti-tumor immune response in colorectal cancer. - Dandong Dai;You Yin;Yuanbo Hu;Ying Lu;Hongbo Zou;GuangZhao Lu;Qianqian Wang;Jie Lian;Jie Gao;Xian Shen - Drug delivery (2021)
  7. A review on the advances and challenges of immunotherapy for head and neck cancer. - Gang Cheng;Hui Dong;Chen Yang;Yang Liu;Yi Wu;Lifen Zhu;Xiangmin Tong;Shibing Wang - Cancer cell international (2021)
  8. [SARS-CoV-2-update on skin manifestations, predictive markers and cutaneous reactions after vaccination]. - Katharina Antonia Drerup;Regine Gläser - Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete (2021)
  9. Critical View of Novel Treatment Strategies for Glioblastoma: Failure and Success of Resistance Mechanisms by Glioblastoma Cells. - Timo Burster;Rebecca Traut;Zhanerke Yermekkyzy;Katja Mayer;Mike-Andrew Westhoff;Joachim Bischof;Uwe Knippschild - Frontiers in cell and developmental biology (2021)
  10. Therapeutic cancer vaccines revamping: technology advancements and pitfalls. - G Antonarelli;C Corti;P Tarantino;L Ascione;J Cortes;P Romero;E A Mittendorf;M L Disis;G Curigliano - Annals of oncology : official journal of the European Society for Medical Oncology (2021)

... (409 more literatures)

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