Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189284 - 189284
Published: Feb. 1, 2025
Language: Английский
Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(5), P. 406 - 418
Published: April 12, 2024
T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers have the potential revolutionize therapy many other diseases. To circumvent complexity cost associated with broad-scale implementation of ex vivo manufactured adoptive cell products, alternative strategies generate CAR in by direct infusion nanoparticle-formulated nucleic acids or engineered viral vectors under development received a great deal attention past few years. Here, we outline manufacturing process as motivating framework discuss emerging data from preclinical models highlight potency approach, applicability new disease indications, remaining challenges clinical readiness, including delivery specificity, long term efficacy, safety.
Language: Английский
Citations
23
Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
4
Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11
Published: Jan. 13, 2025
Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As field advances, its transformative potential is now expanding into oncology, where personalized therapies address immune-related complexities cancer. This review highlights innovative therapeutic strategies, including gene replacement, silencing, oncolytic virotherapy, CAR-T cell therapy, CRISPR-Cas9 editing, with focus on their application both hematologic malignancies solid tumors. CRISPR-Cas9, revolutionary tool precision medicine, enables precise editing cancer-driving mutations, enhancing immune responses disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form death—offering new possibilities for selectively inducing death resistant cancers. Despite significant breakthroughs, challenges such as heterogeneity, evasion, immunosuppressive microenvironment (TME) remain. To overcome these barriers, novel like dual-targeting, armored cells, combination checkpoint inhibitors ferroptosis inducers are being explored. rise allogeneic “off-the-shelf” offers scalable more accessible options. The regulatory landscape evolving accommodate advancements, frameworks RMAT (Regenerative Medicine Advanced Therapy) U.S. ATMP (Advanced Therapy Medicinal Products) Europe fast-tracking approval therapies. However, ethical considerations surrounding CRISPR-based editing—such off-target effects, germline ensuring equitable access—remain at forefront, requiring ongoing oversight. Advances non-viral delivery systems, lipid nanoparticles (LNPs) exosomes, improving safety efficacy By integrating innovations addressing concerns, poised revolutionize cancer treatment, providing durable, effective,
Language: Английский
Citations
3
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: June 19, 2024
Chimeric antigen receptor (CAR) T-cell therapy has proven a breakthrough in cancer treatment the last decade, giving unprecedented results against hematological malignancies. All approved CAR products, as well many being assessed clinical trials, are generated using viral vectors to deploy exogenous genetic material into T-cells. Viral have long-standing history gene delivery, and thus underwent iterations of optimization improve their efficiency safety. Nonetheless, capacity integrate semi-randomly host genome makes them potentially oncogenic via insertional mutagenesis dysregulation key cellular genes. Secondary cancers following administration appear be rare adverse event. However several cases documented few years put spotlight on this issue, which might been underestimated so far, given relatively recent deployment therapies. Furthermore, initial successes obtained malignancies not yet replicated solid tumors. It is now clear that further enhancements needed allow T-cells increase long-term persistence, overcome exhaustion cope with immunosuppressive tumor microenvironment. To aim, variety genomic engineering strategies under evaluation, most relying CRISPR/Cas9 or other editing technologies. These approaches liable introduce unintended, irreversible alterations product cells. In first part review, we will discuss non-viral used for generation T-cells, whereas second focus non-gene engineering, particular regard advantages, limitations, Finally, critically analyze different combinations, delineating superior safety profile production next-generation T-cell.
Language: Английский
Citations
10
Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)
Published: May 14, 2024
CAR NK cells as vehicles for engineered "off-the-shelf" cellular cancer immunotherapy have attracted significant interest. Nonetheless, a comprehensive comparative assessment of the anticancer activity T and carrying approved benchmark anti-CD19 constructs is missing. Here, we report direct head-to-head comparison CD19-directed human cells. We generated derived from healthy donor PBMC by retroviral transduction with same second-generation construct, FMC63.28z. investigated IFN-γ secretion cytotoxicity in vitro against various CD19+ cell lines well autologous versus allogeneic settings. Furthermore, assessed vivo using xenograft lymphoma model an setting leukemia model. Our main findings are drastically reduced capacity CAR-mediated production lower relative to vitro. Consistent these findings, superior compared vivo. had significantly higher effector functions than several outperformed both will likely benefit further engineering enhance ultimately fulfill promise effective off-the-shelf product.
Language: Английский
Citations
9
Trends in biotechnology, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Autologous chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment and allogeneic CAR-T is poised to advance this revolution. faces some concerns regarding adventitious agents, which can threaten the safety of patients. Human herpesviruses 6 7 (HHV-6 HHV-7) have become increasingly notable in context, as they carry a risk with severe health consequences. This review explores these virus reactivations discusses mitigation strategies during manufacturing. We provide an overview prevention testing strategies, genetic engineering applications, chemical substances potential for interventions. aims enhance understanding HHV reactivation improve therapies.
Language: Английский
Citations
1
Cureus, Journal Year: 2024, Volume and Issue: unknown
Published: July 24, 2024
Chimeric antigen receptor T (CAR-T) cell therapy has transformed the field of immunology by redirecting lymphocytes toward tumor antigens. Despite successes in attaining high remission rates as 90%, performance CAR is limited survival cells. persistence crucial it sustains immune response against malignancies, playing a critical role cancer treatment outcomes. This review explores various approaches to improve CAR-T persistence, focusing on choice between autologous and allogeneic sources, optimization culture conditions for subsets, metabolite adjustments modify metabolism, use oncolytic viruses (OVs), advancements design. Autologous cells generally exhibit longer but are less accessible cost-effective than their counterparts. Optimizing promoting
Language: Английский
Citations
6
Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(771)
Published: Oct. 30, 2024
Chimeric antigen receptor–T cell (CAR-T) therapy has transformed the management of refractory hematological malignancies. Now that targeting pathogenic cells interest with antigen-directed cytotoxic T lymphocytes is possible, field expanding reach CAR-T beyond oncology. Recently, breakthrough progress been made in application technology to autoimmune diseases, exploiting same validated targets were used by pioneering therapies hematology. Here, we discuss recent advances and outcomes are paving way for extension new therapeutic areas, including autoimmunity.
Language: Английский
Citations
6
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9518 - 9518
Published: Sept. 1, 2024
Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR products been approved Food Drug Administration (FDA) for treatment relapsed/refractory B-cell multiple myeloma. The indications are gradually expanding, these being investigated a variety diseases, including non-malignant ones. Despite great success, there several challenges surrounding therapies, such as non-durable responses high-grade toxicities. In addition, new safety concern was added FDA on 28 November 2023 following reports previously treated either or autologous both clinical trials real-world setting. Since then, published presenting incidence analysing risks other secondary after therapies. this opinion article, current landscape is presented, along proposed strategy future research aiming at potentially diminishing abrogating risk developing
Language: Английский
Citations
5
Small Science, Journal Year: 2024, Volume and Issue: unknown
Published: July 30, 2024
Lipid nanoparticles and polymeric are promising biomaterial platforms for robust intracellular DNA mRNA delivery, highlighted by the widespread use of nanoparticle‐ (NP) based vaccines to help end COVID‐19 pandemic. Recent research has sought adapt this nanotechnology transfect engineer immune cells in vivo. The system is an especially appealing target due its involvement many different diseases, ex vivo‐engineered cell therapies like chimeric antigen receptor (CAR) T therapy have already demonstrated remarkable clinical success certain blood cancers. Although gene delivery can potentially address some cost manufacturing concerns associated with current autologous therapies, transfecting vivo challenging. Not only extrahepatic NP lymphoid organs difficult, but particular resistance transfection. Despite these challenges, modular nature NPs allows researchers examine critical structure–function relationships between a particle's properties ability specifically Herein, several nanomaterial components outlined, including targeting ligands, nucleic acid cargo, chemical properties, physical route administration optimal
Language: Английский
Citations
4