Cytotherapy, Journal Year: 2023, Volume and Issue: 25(6), P. 670 - 682
Published: Feb. 26, 2023
Chimeric antigen receptor (CAR) T cells have demonstrated remarkable efficacy against hematological malignancies; however, they not experienced the same success solid tumors such as glioblastoma (GBM). There is a growing need for high-throughput functional screening platforms to measure CAR T-cell potency tumor cells.
Language: Английский
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: June 9, 2022
Adoptive transfer of chimeric antigen receptor (CAR) T lymphocytes is a powerful technology that has revolutionized the way we conceive immunotherapy. The impressive clinical results complete and prolonged response in refractory relapsed diseases have shifted landscape treatment for hematological malignancies, particularly those lymphoid origin, opens up new possibilities solid neoplasms. However, widening use cell therapy hampered by accessibility to viral vectors are commonly used transfection. In era messenger RNA (mRNA) vaccines CRISPR/Cas (clustered regularly interspaced short palindromic repeat–CRISPR-associated) precise genome editing, novel virus-free methods engineering emerging as more versatile, flexible, sustainable alternative next-generation CAR manufacturing. Here, discuss how non-viral can address some limitations gene allow us deliver genetic information stable, effective straightforward manner. particular, main transposon systems such Sleeping Beauty (SB) piggyBac (PB), utilization mRNA, innovative approaches nanotechnology like Lipid-based Polymer-based DNA nanocarriers nanovectors. We also describe most relevant preclinical data recently led trials, related safety efficacy aspects. will provide practical considerations future trials enable successful safe with generation.
Language: Английский
Citations
96
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
Citations
19
Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102457 - 102457
Published: Jan. 18, 2025
Language: Английский
Citations
3
Immuno-Oncology Technology, Journal Year: 2023, Volume and Issue: 18, P. 100375 - 100375
Published: March 9, 2023
Language: Английский
Citations
39
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: March 15, 2024
Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance repair of neural tissue well-established, functions during normal organism development remain understudied. Meanwhile, studies have shown that plays an important tumorigenesis. Its include proliferation, invasion, motility, metastasis, high ability transform microenvironment may be associated malignant phenotype. Structurally, glycosphingolipid stably expressed on surface cells, making it suitable candidate targeting by antibodies or chimeric antigen receptors. Based mouse monoclonal antibodies, humanized their combinations cytokines, toxins, drugs, radionuclides, nanoparticles as well receptor been developed. Furthermore, vaccines photoimmunotherapy are being used treat GD2-positive tumors, aptamers can targeting. In field cell therapy, allogeneic immunocompetent cells also utilized enhance therapy. Efforts currently made optimize modifying design transducing not only αβ T but γδ NK NKT macrophages. addition, combine both diagnostic therapeutic methods, allowing early detection disease minimal residual disease. This review discusses each method strategy, advantages disadvantages, highlights future directions
Language: Английский
Citations
14
Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)
Published: May 6, 2023
Abstract Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding immunology oncology. In this review, we summarize recent applications single-cell technologies CAR therapy, including biological characteristics, latest response adverse events, promising strategies that contribute to development target selection. Generally, propose a multi-omics research mode guide potential future on therapy.
Language: Английский
Citations
22
Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)
Published: June 26, 2023
Abstract Background Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma malignancies could disrupt the therapeutic landscape solid tumors. However, access to CAR-T is not adequate meet clinical needs, in part due high cost long lead times manufacturing grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 double-stranded DNA (dsDNA) or single-stranded (ssDNA) via homology-directed repair (HDR), however yields this approach have been limiting application large sufficient demands outside early phase trials limited (ssDNA). Methods We applied homology-independent targeted insertion (HITI) HDR nanoplasmid insert an anti-GD2 into receptor alpha constant (TRAC) locus compared both strategies our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) seamlessly integrate it a 14-day process knock-in viral transduced cells. Finally, explored off-target genomic toxicity engineering approach. Results Here, show that utilizing delivered HITI provides highly functional CEMENT enriched approximately 80% purity, resulting therapeutically relevant dose ranges 5.5 × 10 8 –3.6 9 + were functionally comparable did any evidence toxicity. Conclusions Our work novel platform perform guided primary human T-cells holds potential increase therapies.
Language: Английский
Citations
20
Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 119 - 119
Published: Jan. 6, 2024
T lymphocytes represent a promising target for genome editing. They are primarily modified to recognize and kill tumor cells or withstand HIV infection. In most studies, cell editing is performed using the CRISPR/Cas technology. Although this technology easily programmable widely accessible, its efficiency of was initially low. Several crucial improvements were made in components their delivery methods, as well culturing conditions cells, before reasonable level suitable clinical applications achieved. review, we summarize describe aforementioned parameters that affect human technology, with special focus on gene knock-in.
Language: Английский
Citations
6
Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(2), P. 101249 - 101249
Published: April 10, 2024
Manufacturing chimeric antigen receptor (CAR) T cell therapies is complex, with limited understanding of how medium composition impacts phenotypes. CRISPR-Cas9 ribonucleoproteins can precisely insert a CAR sequence while disrupting the endogenous alpha constant (
Language: Английский
Citations
6
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: May 30, 2024
Abstract Target cancer therapy has been developed for clinical treatment based on the discovery of CRISPR (clustered regularly interspaced short palindromic repeat) -Cas system. This forefront and cutting-edge scientific technique improves research into molecular level is currently widely utilized in genetic investigation precision therapy. In this review, we summarized modification by CRISPR/Cas screening system, discussed key components successful screening, including Cas enzymes, guide RNA (gRNA) libraries, target cells or organs. Furthermore, focused application CAR-T cell therapy, drug target, selection both ex vivo with addition, elucidated advantages potential obstacles system medicine described prospects future summary, provide a comprehensive practical perspective development defects, aiming to further improve accuracy individualized gene
Language: Английский
Citations
5