TCR-T cell therapy for solid tumors: challenges and emerging solutions

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

With the use of T cell receptor cells (TCR-T cells) and chimeric antigen (CAR-T cells), T-cell immunotherapy for cancer has advanced significantly in recent years. CAR-T therapy demonstrated extraordinary success when used to treat hematologic malignancies. Nevertheless, there are several barriers that prevent this achievement from being applied solid tumors, such as challenges with tumor targeting inadequate transit adaption genetically modified T-cells, especially unfavorable microenvironments The deficiencies treatment tumors compensated by TCR-T cells, which have a stronger homing ability initiate intracellular commands, 90% proteins can be developmental targets, they recognize target antigens more broadly. As result, may effective treating tumors. In review, we discussed structure outlined drawbacks therapy, suggested potential remedies. This review is crucial understanding current state future therapy. We emphasize how important it combinatorial approaches, combining new combinations various emerging strategies over-the-counter therapies designed TCR-T, increase anti-tumor efficacy inside TME maximize safety, comes immunotherapies.

Language: Английский

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A strategy for synergistic enhancement of immune circulation in head and neck squamous cell carcinoma by novel nucleic acid drug therapy and immunotherapy

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 20, 2025

Studies have shown that in the pathogenesis of head and neck squamous cell carcinoma, immune circulation obstruction caused by various factors including metabolic abnormalities, gene mutations, matrix barrier, is a critical factor for induction tumor development progression. Therefore, immunotherapy strategy killing carcinoma cells an enhanced mechanism has attracted much attention. In addition, rapid new nucleic acid drug therapy, such as mRNA, oligonucleotide small guide RNA (sgRNA), taken (immune checkpoint inhibitors, vaccines, cellular immunotherapy, cytokines adjuvants, etc.) to level. The combination therapy with developed its therapeutic properties brought direction diagnosis treatment two had considerable curative effect patients refractory/recurrent carcinoma. this review, we summarized latest progress applied conventional discussed action efficacy, looked into future trend.

Language: Английский

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In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3119 - 3119

Published: March 28, 2025

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized cancer immunotherapy but continues to face significant challenges that limit its broader application, such as targeting, the tumor microenvironment, and persistence, especially in solid tumors. Meanwhile, global implementation of mRNA vaccines during COVID-19 pandemic highlighted transformative potential lipid nanoparticle (LNP) technologies. These innovations, characterized by their swift development timelines, precise design, efficient delivery mechanisms, provide a promising framework address some limitations CAR-T therapy. Recent advancements, including mRNA-based CAR engineering optimized LNP delivery, have demonstrated capacity enhance efficacy, particularly context This review explores how mRNA-LNP technology can drive vivo engineered therapies current discusses future directions, advancements optimization, strategies for improving functionality safety. By bridging these technological insights, may evolve into versatile accessible treatment paradigm across diverse oncological landscapes.

Language: Английский

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Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 844 - 844

Published: April 1, 2025

Background/Objectives: The AXL receptor tyrosine kinase is a promising therapeutic target in solid tumors, yet conventional viral vector-engineered CAR-T cells face critical limitations, including risks of insertional mutagenesis and immunogenicity from murine-derived single-chain variable fragments (scFvs). This study aimed to develop evaluate mRNA-engineered fully human (mfhAXL CAR-T) as safer, scalable alternative for tumor immunotherapy. Methods:mfhAXL were generated via electroporation-mediated delivery vitro transcribed mRNA encoding AXL-specific CAR. CAR expression kinetics T-cell viability quantified by flow cytometry. Antitumor activity was assessed through co-cultures with AXL-positive lung pancreatic cancer cells, measuring cytotoxicity, cytokine secretion, specificity. In vivo efficacy evaluated xenograft mouse model, volume body weight monitored over 14 days. Results: Flow cytometry confirmed transient but high (>90% at 24 h) preserved (>90%). vitro, mfhAXL exhibited dose-dependent cytotoxicity antigen-specific secretion. vivo, four administrations suppressed growth without loss. Conclusions: mRNA-electroporated platform enables cost-effective, large-scale production, offering safer vector-based approaches eliminating immunogenicity.

Language: Английский

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Engineering Lipid Nanoparticles for mRNA Immunotherapy

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2025, Volume and Issue: 17(2)

Published: March 1, 2025

ABSTRACT Over the last decades, messenger RNA (mRNA) has emerged as a promising therapeutic modality, enabling delivery of genetic instructions to cells for producing proteins or antigens. As such, mRNA‐based therapies can be developed wide range conditions, including infections, cancer, metabolic disorders, and diseases. Nevertheless, using mRNA therapeutically requires chemical modifications reduce immunostimulatory effects nanotechnology prevent degradation ensure intracellular delivery. Lipid nanoparticles (LNPs) have become most effective platform therapeutics, which are primarily employed vaccine purposes following local administration hepatic applications systemic administration. Here, we review state‐of‐the‐art LNP‐mRNA technology discuss its potential immunotherapy. We first outline requirements used therapeutically, role LNP‐mediated Next, highlight immunotherapy approaches vaccination, immuno‐oncology, autoimmune disorders. In addition, challenges that limiting LNP‐mRNA's widespread use, tunable biodistribution effects. Finally, provide an outlook on how implementing such library screening machine learning will guide development next‐generation therapeutics.

Language: Английский

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