A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Language: Английский

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Epigenome editing technologies for discovery and medicine

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(8), P. 1199 - 1217

Published: July 29, 2024

Language: Английский

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CRISPR–Cas9 applications in T cells and adoptive T cell therapies

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: April 12, 2024

Abstract T cell immunity is central to contemporary cancer and autoimmune therapies, encompassing immune checkpoint blockade adoptive therapies. Their diverse characteristics can be reprogrammed by different challenges dependent on antigen stimulation levels, metabolic conditions, the degree of inflammation. cell-based therapeutic strategies are gaining widespread adoption in oncology treating inflammatory conditions. Emerging researches reveal that clustered regularly interspaced palindromic repeats–associated protein 9 (CRISPR–Cas9) genome editing has enabled cells more adaptable specific microenvironments, opening door advanced therapies preclinical clinical trials. CRISPR–Cas9 edit both primary engineered cells, including CAR-T TCR-T, vivo vitro regulate differentiation activation states. This review first provides a comprehensive summary role its applications studies for We also explore application CRISPR screen high-throughput technology anticipate current limitations CRISPR–Cas9, off-target effects delivery challenges, envisioned improvements related technologies disease screening, diagnosis, treatment.

Language: Английский

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Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 6, 2022

Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, immunosuppression. One the most common RNA N6-methyladenosine (m 6 A) methylation, widely involved regulation physiological pathological processes, including development. Compelling evidence indicates that m A methylation regulates transcription protein expression through shearing, export, translation, processing, thereby participating dynamic evolution TME. Specifically, methylation-mediated adaptation to phenotypic shift immune cells synergistically promote formation an immunosuppressive supports proliferation metastasis. In this review, we have focused on involvement tumor-adaptive described detailed linking change cell biological functions. view collective data, advocate treating as complete ecosystem components crosstalk with each other achieve adaptive changes. Finally, describe potential utility methylation-targeted therapies immunotherapy clinical applications challenges faced, aim advancing research.

Language: Английский

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Multiplex base- and prime-editing with drive-and-process CRISPR arrays

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 19, 2022

Abstract Current base- and prime-editing technologies lack efficient strategies to edit multiple genomic loci simultaneously, limiting their applications in complex genomics polygenic diseases. Here, we describe drive-and-process (DAP) CRISPR array architectures for multiplex base-editing (MBE) (MPE) human cells. We leverage tRNA as the RNA polymerase III promoter drive expression of tandemly assembled tRNA-guide (gRNA) arrays, which individual gRNAs are released by cellular endogenous processing machinery. engineer a 75-nt cysteine (hCtRNA) DAP array, achieving up 31-loci MBE 3-loci MPE. By applying or MPE elements deliveries via adeno-associated virus (AAV) lentivirus, demonstrate simultaneous editing disease-relevant loci. Our work streamlines on single establishes biomedical research therapeutic applications.

Language: Английский

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Strategies to enhance CAR-T persistence

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 23, 2022

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved the life expectancy for patients with refractory or relapse B lymphoma. As acute lymphoblastic leukemia (B-ALL), although primary response rate is promising, high incidence of early caused modest long-term survival CAR-T alone. One main challenges limited persistence cells. To further optimize clinical effects cells, many studies have focused on modifying CAR structure and regulating differentiation. In this review, we focus summarize latest progress strategies adopted during in vitro culture stage to immunotherapy by improving persistence. Such include choosing a suitable source, conditions, combining cells conventional drugs, applying genetic manipulations, all which may improve hematologic malignancies reducing probability recurrence after infusion provide clues solid tumor development.

Language: Английский

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CRISPR screens for functional interrogation of immunity

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 363 - 380

Published: Dec. 8, 2022

Language: Английский

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Time-resolved single-cell RNA-seq using metabolic RNA labelling

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Sept. 29, 2022

Language: Английский

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A T cell resilience model associated with response to immunotherapy in multiple tumor types

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(7), P. 1421 - 1431

Published: May 2, 2022

Language: Английский

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Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS

Nature, Journal Year: 2023, Volume and Issue: 614(7947), P. 334 - 342

Published: Jan. 25, 2023

Language: Английский

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