Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)
Published: Sept. 19, 2024
Language: Английский
Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
1
Biotechnology Progress, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 23, 2025
Abstract Cell and gene therapy (CGT) products are emerging innovative biopharmaceuticals that hold promise for treating diseases otherwise beyond the scope of conventional medicines. The evolution CGT from a research idea to promising therapeutic product is due complementary advancements across various scientific disciplines. First, innovations in editing delivery technology have provided fundamental tools manipulate genes cells pursuits. Second, applied translational research, including how clinical trials designed, performed, evaluated, analyzed, transformed into potential product. Third, scaling up production been critical delivering preclinical studies, trials, approved treatments. In parallel, regulatory requirements continuously evolved, with lessons learned studies biomanufacturing. These combined efforts concept reality treat wide range diseases. However, continued R&D oversight crucial further improve safety, efficacy, accessibility products.
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 11, 2025
This work examines the anticancer activity, anti-inflammatory nature, and cytotoxicity of ethanol extract obtained from female flowers Cannabis sativa L using molecular methods in vitro , animal testing vivo as well computational simulations silico . From GC-MS analysis, following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), humulene. The antiproliferative activities determined on HeLa cells by MTT, Crystal Violet, Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality. bioinformatics analysis docking proved significant ligand-protein interactions CBD, THC, humulene cancer-associated proteins such PD-1/PD-L1, TNF-α, MMP-9. In breast cancer was first established Sprague-Dawley rats 7,12-dimethylbenz(a)anthracene (DMBA) then treated cannabinoids either singularly or combination. Detailed treatment demonstrated that use three simultaneously yielded best outcomes together tumor reduction. concentration serum biomarkers inflammation progression substantially reduced groups compared to control group, which proves synergistic effects these therapy. study emphasizes importance medical derivatives treatment.
Language: Английский
Citations
0
Theranostics, Journal Year: 2025, Volume and Issue: 15(8), P. 3345 - 3367
Published: Feb. 18, 2025
Inspired by the remarkable success of CAR-T therapy in hematologic malignancies, research is increasingly focused on adapting this treatment for solid tumors. However, efficacy remains limited due to its exhaustion and shortened persistence. Transcription factors epigenetic modifications play pivotal roles modulating T cell differentiation functionality, which have been leveraged numerous strategies promote formation long-lasting memory cells with stem-like properties supercharging performance. This review highlights transcriptional factors, such as c-Jun FOXO1, enhance sustain effector function, diminishes exhaustion, regulators like TET2 DNMT3A, whose knockout promotes subsets formation. We explore their interconnections, downstream targets, biological impacts, potential application risks certain candidates, providing a comprehensive theoretical framework therapies through interventions.
Language: Английский
Citations
0
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114412 - 114412
Published: March 7, 2025
Language: Английский
Citations
0
Immunobiology, Journal Year: 2025, Volume and Issue: unknown, P. 152888 - 152888
Published: March 1, 2025
Ovarian and gastric cancers, representative of many solid tumors, remain among the most challenging malignancies to treat due limited therapeutic options poor outcomes at advanced stages. Although immunotherapies have revolutionized cancer treatment, their efficacy in tumors has been hindered by issues such as antigen heterogeneity immunosuppressive tumor microenvironment. This study presents development evaluation third-generation chimeric receptor T (CAR-T) cells targeting B7-H3, an immune checkpoint molecule widely overexpressed tumors. The B7-H3 CAR-T exhibited robust selective cytotoxicity against B7-H3-positive cells, sparing normal tissues. In preclinical animal models, these significantly inhibited growth, demonstrating higher specificity preferential accumulation sites. These results highlight B7-H3-targeted a potential breakthrough immunotherapy for offering foundation future clinical trials refine safety efficacy.
Language: Английский
Citations
0
Metabolic Engineering, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Citations
0
Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(4)
Published: April 1, 2025
Language: Английский
Citations
0
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
3
Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(2), P. 101261 - 101261
Published: May 24, 2024
As of March 2024, the U.S. Food and Drug Administration has approved 36 cell gene therapy products,1https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products.Google Scholar numerous others are currently under evaluation in clinical trials. This rapidly evolving field offers innovative therapeutic options for patients suffering from severe genetic acquired diseases. However, as development pre-clinical evaluations these promising new therapies expand, there is a significant need improved production methods techniques that reproducible2Abou-El-Enein M. Angelis A. Appelbaum F.R. Andrews N.C. Bates S.E. Bierman A.S. Brenner M.K. Cavazzana Caligiuri M.A. Clevers H. et al.Evidence generation reproducibility research: A call to action.Mol. Ther. Methods Clin. Dev. 2021; 22: 11-14Google adhere Good Manufacturing Practices (GMP) standards. step critical assessing efficacy safety human Particularly, among principal challenges widespread implementation complexity scalability manufacturing processes required wide array products.3Abou-El-Enein Elsallab Feldman S.A. Fesnak A.D. Heslop H.E. Marks P. Till B.G. Bauer G. Savoldo B. Scalable CAR T cells Cancer Immunotherapy.Blood Discov. 2: 408-422Google Each requires comprehensive rigorous analytical quality control. Multiple variables can influence comparative performance products, necessitating each process be individually analyzed. analysis focuses on its impact yield, purity, which daunting task. In response challenges, advancements innovations have been made several key areas streamline scaling therapies. One foundational components approaches involve use viral vectors, bioengineered viruses designed deliver genes into patient cells. The engineering vectors crucial, it involves modification virus carry while ensuring cannot replicate way causes disease or other unwanted side effects. Enhancement used produce purify major focus with aim increasing their safety, transduction efficiency, scalability. Parallel methods, non-viral delivery such electroporation (using electrical pulses introduce DNA, RNA, proteins cells), lipid-based nanoparticles, naked DNA mRNA injections provide alternative pathways mitigate some risks associated immune activation potential mutagenesis. Additionally, expansion platforms crucial producing at doses. These allow growth carefully controlled conditions. Importantly, comes cost, integration automation technologies biomanufacturing maintaining consistency, decreasing error, enhancing efficiency. special issue Molecular Therapy - Clinical Development therapy. It dedicated all aspects includes selected series review research articles commissioned by our editorial team. also features collection primary papers submitted this theme. While study within contributed significantly field, due space constraints, we selectively highlight subset studies. Throughout history therapy, adeno-associated (AAV) instrumental good profile system. New AAV capsids designer tissue tropisms continually being described validated therapeutics models disease. Simultaneously, vector evolved scientific advancements, focusing optimizing quality. issue, Mevel al.4Mevel Pichard V. Bouzelha Alvarez-Dorta D. Lalys P.A. Provost N. Allais Mendes Landagaray E. Ducloyer J.B. al.Mannose-coupled AAV2: second-generation increased retinal efficiency.Mol. 2024; 32101187Google present advancement AAV-based By covalently attaching mannose ligand amino acids capsid, researchers were able substantially enhance rat nonhuman primate retinas. reduces necessary dosage minimizes therapy-directed responses observed higher Building theme optimization, Mietzsch colleagues novel composed solely VP3 proteins.5Mietzsch Liu W. Ma K. Bennett Nelson A.R. Gliwa Chipman Fu X. Bechler S. McKenna R. Viner Production characterization an AAV1-VP3-only capsid: An benchmark standard.Mol. 2023; 29: 460-472Google capsid serves high-quality standard biophysical assays, ion exchange chromatography native mass spectrometry, providing homogeneous high molecular weight standard. tool aids refining accurate measurement physical chemical properties control production. Similarly, Marwidi al.6Marwidi Y. Nguyen H.O.B. Santos Wangzor T. Bhardwaj Ernie Prawdzik Lew Shivak Trias al.A robust flexible baculovirus-insect system ratios potency.Mol. 32101228Google enhances using baculovirus-based called SGMO Helper. Developed AAV6 demonstrates yields, better integrity, greater resistance proteolytic degradation compared previous methods. Further capabilities, Heckel al.7Heckel J. Martinez Elger C. Haindl Leiss Ruppert Williams Hubbuch Graf Fast HPLC-based affinity method determine titer full/empty ratio vectors.Mol. 31101148Google rapid affinity-based high-performance liquid less than 5 min. addresses complex time-consuming nature traditional Last, Rodgers al.8Rodgers B.D. Herring S.K. Carias D.R. Chen Rocha A.G. validation model biodistribution assay AVGN7 digital droplet polymerase chain reaction.Mol. 494-503Google PCR-based studies Smad7 therapeutic, AVGN7, utilizing serotype targeting muscle wasting enables absolute quantification sensitivity adaptable Investigational applications, bridging gap regulatory guidance quantification. Other technology, notably through refinement lentiviral, retroviral advancing cancer treatment, applications. Bastone al.9Bastone A.L. Dziadek John-Neek Mansel F. Fleischauer Agyeman-Duah Schaudien Dittrich-Breiholz O. Schwarzer Schambach Rothe vitro genotoxicity detect vector-induced lymphoid insertional mutants.Mol. 30: 515-533Google address concerns known risk mutagenesis led leukemia recipients.9Bastone Scholar,10Hacein-Bey-Abina Von Kalle Schmidt McCormack M.P. Wulffraat Leboulch Lim Osborne C.S. Pawliuk Morillon al.LMO2-associated clonal proliferation two after SCID-X1.Science. 2003; 302: 415-419Google They developed murine hematopoietic stem progenitor harmful mutations induced particularly those affecting aims improve identifying potentially oncogenic changes early process. Malach al.11Malach Kay Tinworth Patel Joosse Wade Rosa do Carmo Donovan Brugman Montiel-Equihua Francis Identification small molecule lentiviral cells.Mol. 31101113Google detail discovery optimization improves efficiency Through high-throughput screen more 27,000 compounds, six candidates identified further clinical-grade vectors. lead compound demonstrated enhanced without compromising viability function enabled reduction volume vector. attempt optimize production, Stibbs explore continuous stable producer line fixed-bed bioreactor.12Stibbs D.J. Silva Couto Takeuchi Rafiq Q.A. Jackson N.B. Rayat A.C.M.E. Continuous bioreactor.Mol. 32101209Google Their maintain over extended periods. help bottlenecks previously encountered manufacture Recent advances cellular therapies, especially chimeric antigen receptor (CAR) cell, (TCR), (HSC)-based shown results treatment various malignancies disorders. Poletti al.13Poletti Montepeloso Pellin Biffi Prostaglandin E2 enhancer affects competitive engraftment 31101131Google explored prostaglandin HSCs. did reduced clonogenic CD34+ cells, presenting disadvantage repopulation assays. emphasized importance weighing benefits when selecting reagents. Asperti al.14Asperti Canarutto Porcellini Sanvito Cecere Vavassori Ferrari Rovelli Albano L. Jacob al.Scalable GMP-compliant correction CD4+ IDLV template functionally vivo.Mol. 546-557Google develop integrase-defective editing effectiveness treating hyper-IgM1, immunodeficiency. similar vein, Lydeard al.15Lydeard J.R. Lin M.I. Ge H.G. Halfond Wang Jones M.B. Etchin Angelini Xavier-Ferrucio Lisle al.Development edited next-generation transplant enable acute myeloid solving off-tumor toxicity.Mol. 31101135Google employ CRISPR/Cas9 edit HSPCs (AML), creating product myelotoxic effects CD33-targeted shows 70% CD33 modification, maintains viability, exhibits Song al.16Song H.W. Benzaoui Dwivedi Underwood Shao Achar Posarac Remley V.A. Prochazkova Cai al.Manufacture CD22 following positive versus negative selection distinct cytokine secretion profiles gammadelta output.Mol. 32101171Google examine CAR-T show yielded recovery CD3+ enriched γδ final product, might implications anti-tumor reducing toxicity. exploring Cappabianca al.17Cappabianca Pham Forsberg M.H. Bugel Tommasi Lauer Vidugiriene Hrdlicka McHale Sodji Q.H. al.Metabolic priming GD2 TRAC-CAR during promotes memory phenotypes persistence.Mol. 32101249Google "metabolic priming" manufacturing, where activated low glucose/glutamine environment persistence. Yonezawa Ogusuku al.18Yonezawa I.E. Herbel Lennartz Brandes Argiro Fabian Hauck Hoogstraten Veld Hageman al.Automated DeltaNPM1 TCR-engineered AML therapy.Mol. 32101224Google automated AML. culture conditions, team was reduce time 12 8 days, achieving yields clinically relevant numbers phenotype. engineered specific cytotoxicity against both vivo models, paving phase 1/2 trial. part ongoing efforts systems Kitte al.19Kitte Rabel Geczy Park Fricke Koehl U. Tretbar Lipid nanoparticles outperform mRNA-based engineering.Mol. 31101139Google lipid (LNPs) (EP) delivering CAR-mRNA findings demonstrate LNPs improvement EP prolonged persistence expression. We included approval Blay al.20Blay Hardyman Morovic analytics vectors: Considerations cGMP development.Mol. 31101132Google PCR assays detailing technical, biological, challenges. article proposes future directions testing sequencing artificial intelligence. Braun al.21Braun Lange Schatz Long Stanta Gorovits Tarcsa Jawa Yang T.Y. Lembke al.Preexisting antibody therapy: cutoffs companion diagnostic requirements.Mol. 32101217Google discuss detecting pre-existing antibodies determining trial participant eligibility. work provides overview technical considerations involved developing implementing Dias al.22Dias Garcia Agliardi Roddie landscape – lessons past decade 32101250Google decade's current landscape, covering entire initial industrial scaling. translating products hurdles faced academic teams. conclusion, strides exemplify dynamic transformative period biomedical technology development. continues evolve, collaboration between researchers, clinicians, regulators, industry leaders remains paramount surmounting ahead realizing full revolutionizing care. innovation adherence stringent standards, emerging real-world treatments dealing diseases once deemed incurable.
Language: Английский
Citations
2