mRNA Vaccines: The Dawn of a New Era of Cancer Immunotherapy

Deng, Zhuoya; Tian, Yuying; Song, Jian; An, Guangwen; Yang, Penghui

doi:10.3389/fimmu.2022.887125

Cited by 57 publications

(62 citation statements)

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“…The mRNA vaccine transported via lipid nanoparticle enters the APCs to encode the target tumor antigens, which can be presented on the surface of APCs by MHC (also known as HLA in human) to evoke an antitumor response via interactions with TCR 24 . In this study, C1 subtype showed higher expression of HLA, which may have a greater response to the therapy with mRNA vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, mRNA vaccine is highly practicable for targeting tumor-specific antigens as a promising immunotherapy scheme. Currently, dozens of phase 1/2 clinical trials are underway to prove the effectiveness of mRNA vaccines in patients with various types of cancer, including melanoma, lung cancer, pancreatic cancer, colorectal cancer, ovarian cancer, prostate cancer and relapsed/refractory lymphoma 24 . However, no effective mRNA vaccine for AML has been developed so far.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development

Wang

2022

Preprint

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Background: Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy, and there has not been any significant improvement in therapy of AML over the past several decades. The mRNA vaccines have become a promising strategy against multiple cancers, however, its application on AML remains undefined. In this study, we aimed to identify novel antigens for developing mRNA vaccines against AML and explore the immune landscape of AML to select appropriate patients for vaccination. Methods: The genomic data and clinical information were retrieved from TCGA and GEO, respectively. The gene mutation data of AML were obtained from cBioPortal. GEPIA2 was used to analyze differentially expressed genes. The single cell RNA-seq database Tumor Immune Single-cell Hub (TISCH) was used to explore the association between the potential tumor antigens and the infiltrating immune cells in the bone marrow. Consensus clustering analysis was applied to identify distinct immune subtypes. The correlation between the abundance of antigen presenting cells and the expression level of antigens was evaluated using Spearman correlation analysis. The characteristics of the tumor immune microenvironment in each subtype were investigated based on single-sample gene set enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules and screen the hub genes. Results: Five potential tumor antigens were identified for mRNA vaccine from the pool of overexpressed and mutated genes, including CDH23, LRP1, MEFV, MYOF and SLC9A9, which were associated with infiltration of antigen-presenting immune cells (APCs). AML patients were stratified into two immune subtypes Cluster1 (C1) and Cluster2 (C2), which were characterized by distinct molecular and clinical features. Patients with C1 subtype showed higher expression level of the five candidate genes and worse prognosis compared with C2 subtype. Moreover, C1 subtype demonstrated an immune-hot and immunosuppressive phenotype, while the C1 subtype had an immune-cold phenotype. Furthermore, the two immune subtype showed remarkably different expression of immune checkpoints, immunogenic cell death modulators and human leukocyte antigens. Finally, WCGNA identified a module and five hub genes that can be used for predicting the response of AML patients to mRNA vaccine. Conclusion: CDH23, LRP1, MEFV, MYOF and SLC9A9 were potential antigens for developing AML mRNA vaccine, and AML patients in immune subtype 1 were suitable for vaccination.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development

Wang

2022

Preprint

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“…The outbreak of COVID-19 in 2020 not only boosted the messenger RNA (mRNA) technologies for the development of SARS-CoV-2 vaccine but also renewed interest in mRNA vaccines as an alternative treatment strategy for cancer ( 124 ). In fact, over twenty mRNA-based immunotherapies have entered clinical trials for the treatment of solid tumors, including NSCLC, advanced melanoma, CRC, pancreatic and bladder cancers, and metastatic CEA-expressing solid tumors ( 126 ).…”

Section: Overwhelming Immune Suppressionmentioning

confidence: 99%

“…A cancer vaccine has four key components, the transgene of a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA), the formulation, an immune adjuvant, and the delivery vehicle (123). After vaccine administration, the professional APC (i.e., DCs) processes the antigen, presents it on its surface via MHC molecules, and induces a polyclonal CD4 + and CD8 + T cell response (124)(125)(126). In preclinical studies, cancer vaccines have been shown to inhibit tumor growth and promote TILs while decreasing FoxP3 + Tregs, thereby improving the Teff/Treg ratio (119,(126)(127)(128).…”

Section: Shifting Teff/treg Ratio Through Vaccines and Immunocytokinesmentioning

confidence: 99%

Tipping the scales: Immunotherapeutic strategies that disrupt immunosuppression and promote immune activation

2022

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Immunotherapy has emerged as an effective therapeutic approach for several cancer types. However, only a subset of patients exhibits a durable response due in part to immunosuppressive mechanisms that allow tumor cells to evade destruction by immune cells. One of the hallmarks of immune suppression is the paucity of tumor-infiltrating lymphocytes (TILs), characterized by low numbers of effector CD4+ and CD8+ T cells in the tumor microenvironment (TME). Additionally, the proper activation and function of lymphocytes that successfully infiltrate the tumor are hampered by the lack of co-stimulatory molecules and the increase in inhibitory factors. These contribute to the imbalance of effector functions by natural killer (NK) and T cells and the immunosuppressive functions by myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the TME, resulting in a dysfunctional anti-tumor immune response. Therefore, therapeutic regimens that elicit immune responses and reverse immune dysfunction are required to counter immune suppression in the TME and allow for the re-establishment of proper immune surveillance. Immuno-oncology (IO) agents, such as immune checkpoint blockade and TGF-β trapping molecules, have been developed to decrease or block suppressive factors to enable the activity of effector cells in the TME. Therapeutic agents that target immunosuppressive cells, either by direct lysis or altering their functions, have also been demonstrated to decrease the barrier to effective immune response. Other therapies, such as tumor antigen-specific vaccines and immunocytokines, have been shown to activate and improve the recruitment of CD4+ and CD8+ T cells to the tumor, resulting in improved T effector to Treg ratio. The preclinical data on these diverse IO agents have led to the development of ongoing phase I and II clinical trials. This review aims to provide an overview of select therapeutic strategies that tip the balance from immunosuppression to immune activity in the TME.

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“…Cancer vaccines, which trigger tumor-specific cell-mediated immunity to recognize and kill cancer cells, are one of the most interesting approaches in cancer immunotherapy [1] , [2] , [3] . mRNA-based vaccines are a promising vaccine platform for several reasons [4] , [5] . Firstly, mRNA is delivered into the cytosol for rapid production of large quantity of endogenous protein or peptide antigens, which are processed by the proteasome and presented to the cell surface by the major histocompatibility complex class I (MHC I) to activate CD8 + T cells that are thought to play a key role in the antitumor immunity [6] , [7] , [8] , whereas exogenous peptide/protein antigens are mainly been processed in the lysosome and presented via MHC II, inducing humoral immunity [9] .…”

Section: Introductionmentioning

confidence: 99%

Fluoroalkane modified cationic polymers for personalized mRNA cancer vaccines

Xiang

et al. 2023

Chemical Engineering Journal

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mRNA Vaccines: The Dawn of a New Era of Cancer Immunotherapy

Cited by 57 publications

References 100 publications

Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development

Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development

Tipping the scales: Immunotherapeutic strategies that disrupt immunosuppression and promote immune activation

Fluoroalkane modified cationic polymers for personalized mRNA cancer vaccines

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