Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles

Xiong, Xi; Ke, Xiurong; Wang, Lu; Lin, Yusheng; Wang, Shuhong; Yao, Ziting; Li, Kai; Luo, Yichen; Fan, Lida; Pan, Yunlong; Yeung, Sai‐Ching Jim; Helfrich, Wijnand; Zhang, Hao

doi:10.1002/jev2.12243

Cited by 27 publications

(19 citation statements)

References 69 publications

(88 reference statements)

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“…[541][542][543] In addition to tumor cell-derived EVs, DC-derived EVs can also serve as a neoantigen-presenting unit to immune cells. 544,545 Though modulating the tumor immune microenvironment and systemic immune responses, EV-based vaccination can turn a 'cold' tumor into a 'hot' one. Therefore, EVs may provide an option format for neoantigenbased cancer vaccines, which may potentially be given orally.…”

Section: Determination and Monitoring Of Neoantigen-specific T Cell R...mentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

237

150

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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Section: Determination and Monitoring Of Neoantigen-specific T Cell R...mentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

237

150

View full text Add to dashboard Cite

show abstract

“…For example, Xiong et al discovered a cancer-specific aberrant transcription-induced chimeric RNA encoding A-Pas, a cancer-specific chimeric protein that can modulate the occurrence and EMT of tumors. They used exosomes isolated from chimeric RNA-transfected dendritic cells to construct antitumor vaccines to treat esophagus cancer, resulting in the suppression of cancer and prolonged survival time of mouse models with tumors [ 154 ]. Huang et al prepared the c(RGDyK)-modified engineered exosomes and packaged lncRNA MEG3 into exosomes.…”

Section: The Application Potential Of Rna-loaded Exosomesmentioning

confidence: 99%

Exosome-Based Carrier for RNA Delivery: Progress and Challenges

Huang

et al. 2023

Pharmaceutics

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In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.

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“…[ 102 ] Recently, in a study cell‐free vaccine concept is idealized by incorporating neoantigen‐based cancer vaccine using chimeric RNA‐loaded DC‐derived extracellular vesicle in mice model, which boost CD8+ T cell‐mediated anti‐tumor immunity. [ 103 ] This cell free vaccine approach may provide numerous advantages over cell‐based vaccines but its potential is yet to be discover. In summary, both intranodal delivery and DC‐based mRNA vaccine delivery methods have been shown to be effective approaches for cancer vaccine delivery.…”

Section: Cancer Vaccines—an Overviewmentioning

confidence: 99%

Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach

Goyal,

Chattopadhyay,

Navik

et al. 2023

Advanced Therapeutics

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AbstractmRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to anti‐tumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system have been precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with STING and TLR pathways, activating more CD8+ T‐cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Non‐formulated or vehicle‐based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen‐presenting cells and stimulate both innate and adaptive immune responses. Co‐delivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focused on the current clinical approaches and challenges to consider when developing mRNA‐based vaccine technology for cancer treatment.This article is protected by copyright. All rights reserved

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Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles

Abstract: Development and preclinical evaluation of an extracellular vesicles-based therapeutic cancer vaccine exploiting an immunogenic neoantigen encoded by an aberrant transcription-induced exon-intron antisense chimeric RNA.

Cited by 27 publications

References 69 publications

Neoantigens: promising targets for cancer therapy

Neoantigens: promising targets for cancer therapy

Exosome-Based Carrier for RNA Delivery: Progress and Challenges

Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach

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