T cells to fix a broken heart

Gao, Torahito A; Chen, Yvonne Y.

doi:10.1126/science.abn0851

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…111,112 In numerous research, a therapeutic approach that can produce transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo is developed through the delivery of the modified messenger RNA (mRNA) in T cell-targeted lipid nanoparticles (LNPs), which is called mRNA-based CAR-T cells. 113,114 While mRNA-based CAR-T cells are characterized by rapid, safe, transient, and cost-effective T-cell modification. Meister et al created the multifunctional mRNA-based CAR-T cells which coexpressed NKG2D, IL12, and IFNα2.…”

Section: Multifunctional Mrna-based Car-t Cellsmentioning

confidence: 99%

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma

Liang,

Song,

et al. 2023

IJGM

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Glioblastoma (GBM) is the most common malignant primary brain cancer in adults. It is always resistant to existing treatments, including surgical resection, postoperative radiotherapy, and chemotherapy, which leads to a dismal prognosis and a high relapse rate. Therefore, novel curative therapies are urgently needed for GBM. Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved life expectancy for hematological malignancies patients, and thus it increases the interest in applying CAR-T cell therapy for solid tumors. In the recently published research, it is indicated that there are numerous obstacles to achieve clinical benefits for solid tumors, especially for GBM, because of GBM anatomical characteristics (the blood-brain barrier and suppressive tumor microenvironment) and the tumor heterogeneity. CAR-T cells are difficult to penetrate blood-brain barrier, and immunosuppressive tumor microenvironment (TME), which induces CAR-T cell exhaustion, impairs CAR-T cell therapy response. Moreover, under the pressure of CAR-T cell therapy, the tumor heterogeneity and tumor plasticity drive tumor evolution and therapy resistance, such as antigen escape. Nonetheless, scientists strive for strategies to overcome these hurdles, including novel CAR-T cell designs and regional delivery. For instance, the structure of multi-antigen-targeted CAR-T cells can enrich CAR-T accumulation in tumor TME and eliminate abundant tumor cells to avoid tumor antigen heterogeneity. Additionally, paired with an immune modifier and one or more stimulating domains, different generation of innovations in the structure and manufacturing of CAR-T cells have improved efficacy and persistence. While single CAR-T cell therapy receives limited clinical survival benefit. Compared with single CAR-T cell therapy, the combination therapies have supplemented the treatment paradigm. Combinatorial treatment methods consolidate the CAR-T cells efficacy by regulating the tumor microenvironment, optimizing the CAR structure, targeting the CAR-T cells to the tumor cells, reversing the tumor-immune escape mechanisms, and represent a promising avenue against GBM, based on multiple impressive research. Moreover, exciting results are also reported to be realized through combining effective therapies with CAR-T cells in preclinical and clinical trials samples, have aroused inspiration to explore the antitumor function of combination therapies. In summary, this study aims to summarize the limitation of CAR-T cell therapies and introduces novel strategies to enhance CAR-T cell function as well as prospect the potential of the therapeutic combination.

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Section: Multifunctional Mrna-based Car-t Cellsmentioning

confidence: 99%

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma

Liang,

Song,

et al. 2023

IJGM

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“…Component interventions target upstream risk factors (e.g., hypertension, smoking, etc.) or downstream biomarkers (e.g., cholesterol levels [ 220 , 221 , 222 , 223 , 224 ], myocardial fibrosis [ 225 , 226 , 227 ], macrophage recruitment [ 228 ], arterial blockage, etc.) [ 229 ].…”

Section: Perspective On Optimal Clinical Interventionmentioning

confidence: 99%

A Unified Model of Age-Related Cardiovascular Disease

Fossel

Bean

Khera

et al. 2022

Biology

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Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, affects all components of the cardiovascular system, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, cardiac fibroblasts, and immune cells. The unified model offers insights into the relationship between upstream risk factors and downstream clinical outcomes and explains why interventions aimed at either of these components have limited success. Potential therapeutic approaches are considered based on this model. Because telomerase activity can prevent and reverse cell senescence, telomerase gene therapy is discussed as a promising intervention. Telomerase gene therapy and similar systems interventions based on the unified model are expected to be transformational in cardiovascular medicine.

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“…The combination of CAR T-cell therapy and mRNA vaccine technology avoids some of the potential problems associated with CAR T-cell therapy in the treatment of hematological malignancies. These include the use of viral vectors that alter cellular DNA ( 109 ); T cells need to be harvested from the patient, cultured, and then reintroduced into the patient; the number of T cells that had not been genetically engineered must be reduced by chemotherapy ( 110 ). These combination therapies also extend the potential of mRNA technology beyond vaccines.…”

Section: Mrna Drug Industry Chain and Development Trendmentioning

confidence: 99%

How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

Duan

Zhu

et al. 2022

Front. Immunol.

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mRNA products are therapies that are regulated from the post-transcriptional, pre-translational stage of a gene and act upstream of protein synthesis. Compared with traditional small molecule drugs and antibody drugs, mRNA drugs had the advantages of simple design, short development cycle, strong target specificity, wide therapeutic field, and long-lasting effect. mRNA drugs were now widely used in the treatment of genetic diseases, tumors, and viral infections, and are expected to become the third major class of drugs after small molecule drugs and antibody drugs. The delivery system technology was the key to ensuring the efficacy and safety of mRNA drugs, which plays an important role in protecting RNA structure, enhancing targeting ability, reducing the dose of drug delivery, and reducing toxic side effects. Lipid nanoparticles (LNP) were the most common delivery system for mRNA drugs. In recent years, mRNA drugs have seen rapid development, with the number of drugs on the market increasing each year. The success of commercializing mRNA vaccines has driven a wave of nucleic acid drug development. mRNA drugs were clinically used in genetic diseases, oncology, and infectious diseases worldwide, while domestic mRNA clinical development was focused on COVID-19 vaccines, with more scope for future indication expansion.

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T cells to fix a broken heart

Abstract: In vivo engineered T cells provide a promising approach to treat cardiac diseases

Cited by 5 publications

References 14 publications

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma

A Unified Model of Age-Related Cardiovascular Disease

How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

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