RNA aggregates harness the danger response for potent cancer immunotherapy

Mendez-Gomez, Hector R.; DeVries, Anna; Castillo, Paul; von Roemeling, Christina; Qdaisat, Sadeem; Stover, Brian D.; Xie, Chao; Weidert, Frances; Zhao, Chong; Moor, Rachel; Liu, Ruixuan; Soni, Dhruvkumar; Ogando-Rivas, Elizabeth; Chardon-Robles, Jonathan; McGuiness, James; Zhang, Dingpeng; Chung, Michael C.; Marconi, Christiano; Michel, Stephen; Barpujari, Arnav; Jobin, Gabriel W.; Thomas, Nagheme; Ma, Xiaojie; Campaneria, Yodarlynis; Grippin, Adam; Karachi, Aida; Li, Derek; Sahay, Bikash; Elliott, Leighton; Foster, Timothy P.; Coleman, Kirsten E.; Milner, Rowan J.; Sawyer, W. Gregory; Ligon, John A.; Simon, Eugenio; Cleaver, Brian; Wynne, Kristine; Hodik, Marcia; Molinaro, Annette M.; Guan, Juan; Kellish, Patrick; Doty, Andria; Lee, Ji-Hyun; Massini, Tara; Kresak, Jesse L.; Huang, Jianping; Hwang, Eugene I.; Kline, Cassie; Carrera-Justiz, Sheila; Rahman, Maryam; Gatica, Sebastian; Mueller, Sabine; Prados, Michael; Ghiaseddin, Ashley P.; Silver, Natalie L.; Mitchell, Duane A.; Sayour, Elias J.

doi:10.1016/j.cell.2024.04.003

Cited by 25 publications

(3 citation statements)

References 76 publications

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“…Very recently, Gomez et al. described a new cancer vaccine based on RNA-lipid particle aggregates (RNA-LRP) with expanded loading capacity that allows loading of mRNA encoding for glioma-associated antigens (pp65) and a whole tumor RNA, thus significantly increasing its immunogenicity ( 176 ). This vaccine was delivered i.v.…”

Section: Nucleic Acid Vaccines Against Angiogenic Markersmentioning

confidence: 99%

Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?

Tadic,

Martínez

2024

Front. Immunol.

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Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments.

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Section: Nucleic Acid Vaccines Against Angiogenic Markersmentioning

confidence: 99%

Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?

Tadic,

Martínez

2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…13 The effectiveness of immunotherapy depends largely on the immune status in the tumor microenvironment. 14,15 EMT not only plays an important role in tumor invasion and metastasis but also is closely related to the tumor immune microenviron- ment. Previous studies have shown that EMT can regulate immune escape mechanisms, affecting immune cell infiltration and immune checkpoint molecule expression.…”

Section: ■ Backgroundmentioning

confidence: 99%

Epithelial–Mesenchymal Transition Related Score Functions as a Predictive Tool for Immunotherapy and Candidate Drugs in Glioma

Fu,

Ren,

Dai

et al. 2024

J. Chem. Inf. Model.

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Gliomas are aggressive CNS tumors where the epithelial–mesenchymal transition (EMT) is crucial for prognosis. We developed an EMT-based score predicting overall survival (OS) and conducted pathway analyses, revealing functions such as cell proliferation and immune response in glioma progression. The EMT score, correlated with immune functions and cell infiltration, shows potential as an immune response indicator. We identified two promising compounds, BIX02189 and QL-XI-92, as potential glioma treatments based on candidate gene analysis.

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“…Recently, Mendez-Gomez et al [61] created "onion-like" multi-lamellar RNA lipid particle aggregates (RNA-LPAs) to enhance the immunogenicity of tumor mRNA antigens (synthetic glioma-associated antigens and whole-tumor mRNA). RNA-LPAs reprogrammed the TME towards immunoreaction in GBM animal models and in a phase I human trial with three patients with GBM, detecting increased cytokine/chemokine release and immune activation in the TME.…”

mentioning

confidence: 99%

Pericytes Are Immunoregulatory Cells in Glioma Genesis and Progression

Martinez-Morga,

Garrigos,

Rodriguez-Montero

et al. 2024

IJMS

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Vascular co-option is a consequence of the direct interaction between perivascular cells, known as pericytes (PCs), and glioblastoma multiforme (GBM) cells (GBMcs). This process is essential for inducing changes in the pericytes’ anti-tumoral and immunoreactive phenotypes. Starting from the initial stages of carcinogenesis in GBM, PCs conditioned by GBMcs undergo proliferation, acquire a pro-tumoral and immunosuppressive phenotype by expressing and secreting immunosuppressive molecules, and significantly hinder the activation of T cells, thereby facilitating tumor growth. Inhibiting the pericyte (PC) conditioning mechanisms in the GBM tumor microenvironment (TME) results in immunological activation and tumor disappearance. This underscores the pivotal role of PCs as a key cell in the TME, responsible for tumor-induced immunosuppression and enabling GBM cells to evade the immune system. Other cells within the TME, such as tumor-associated macrophages (TAMs) and microglia, have also been identified as contributors to this immunomodulation. In this paper, we will review the role of these three cell types in the immunosuppressive properties of the TME. Our conclusion is that the cellular heterogeneity of immunocompetent cells within the TME may lead to the misinterpretation of cellular lineage identification due to different reactive stages and the identification of PCs as TAMs. Consequently, novel therapies could be developed to disrupt GBM-PC interactions and/or PC conditioning through vascular co-option, thereby exposing GBMcs to the immune system.

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RNA aggregates harness the danger response for potent cancer immunotherapy

Cited by 25 publications

References 76 publications

Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?

Nucleic acid cancer vaccines targeting tumor related angiogenesis. Could mRNA vaccines constitute a game changer?

Epithelial–Mesenchymal Transition Related Score Functions as a Predictive Tool for Immunotherapy and Candidate Drugs in Glioma

Pericytes Are Immunoregulatory Cells in Glioma Genesis and Progression

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