Inorganic Chemistry Frontiers, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
An oxaliplatin( iv )-maleimide prodrug containing the STING agonist MSA-2 was synthesized with improved pharmacological properties and diminished hematotoxicity. The complex exerted anticancer effects but did not outperform free oxaliplatin or MSA-2.
Язык: Английский
Biomarker Research, Год журнала: 2024, Номер 12(1)
Опубликована: Янв. 7, 2024
Abstract The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing crucial role in improving antitumor immunity through effector responses. Targeting the holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective elimination. However, systemic administration current STING agonists faces challenges related to low bioavailability potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed modulate TMEs robust immunotherapeutic encapsulation delivery within nanoparticles (STING-NPs) present an attractive avenue immunotherapy. This review explores range designed encapsulate agonists, highlighting benefits, including favorable biocompatibility, improved penetration, efficient intracellular agonists. also summarizes immunomodulatory impacts STING-NPs on TME, enhanced secretion pro-inflammatory cytokines chemokines, dendritic cell activation, cytotoxic T priming, macrophage re-education, vasculature normalization. Furthermore, offers insights into co-delivered nanoplatforms involving alongside agents such chemotherapeutic compounds, checkpoint inhibitors, antigen peptides, other adjuvants. These platforms demonstrate remarkable versatility inducing immunogenic responses ultimately amplifying
Язык: Английский
Процитировано
25
Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)
Опубликована: Окт. 10, 2024
Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite improvement multi-modality treatment strategies, prognosis pancreatic was not improved dramatically. For resectable or borderline patients, surgical strategy centered on improving R0 resection rate is consensus; however, role neoadjuvant therapy in patients and optimal chemotherapy with without radiotherapy were debated. Postoperative adjuvant gemcitabine/capecitabine mFOLFIRINOX recommended regardless margin status. Chemotherapy as first-line for advanced metastatic included FOLFIRINOX, gemcitabine/nab-paclitaxel, NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan only standard care second-line therapy. Immunotherapy an innovative although anti-PD-1 antibody currently agent approved by MSI-H, dMMR, TMB-high tumors, which represent very small subset cancers. Combination strategies to increase immunogenicity overcome immunosuppressive tumor microenvironment may sensitize immunotherapy. Targeted therapies represented PARP KRAS inhibitors are also under investigation, showing benefits progression-free survival objective response rate. This review discusses current modalities highlights cancer.
Язык: Английский
Процитировано
21
British Journal of Cancer, Год журнала: 2024, Номер 131(4), С. 627 - 640
Опубликована: Июнь 3, 2024
Tumour-associated macrophages (TAMs) sustain a tumour-supporting and immunosuppressive milieu therefore aggravate cancer prognosis. To modify TAM behaviour unlock their anti-tumoural potential, novel TAM-reprogramming immunotherapies are being developed at an accelerating rate. At the same time, scientific discoveries have highlighted more sophisticated phenotypes with complex biological functions contradictory prognostic associations. understand evolving clinical landscape, we reviewed current past clinically evaluated therapeutics summarised almost 200 agents investigated in than 700 trials. Observable overall trends include high frequency of overlapping strategies against therapeutic targets, development to improve previously ineffective approaches reliance on combinatory for efficacy. However, strong anti-tumour efficacy is uncommon, which encourages re-directing efforts identifying biomarkers eligible patient populations comparing similar treatments earlier. Future endeavours will benefit from considering shortcomings treatment accommodating emerging complexity biology.
Язык: Английский
Процитировано
20
Advanced Healthcare Materials, Год журнала: 2024, Номер 13(20)
Опубликована: Апрель 23, 2024
Abstract Cancer immunotherapy recently transforms the traditional approaches against various cancer malignancies. Immunotherapy includes systemic and local treatments to enhance immune responses involves strategies such as checkpoints, vaccines, modulatory agents, mimetic antigen‐presenting cells, adoptive cell therapy. Despite promising results, these still suffer from several limitations including lack of precise delivery immune‐modulatory agents target cells off‐target toxicity, among others, that can be overcome using nanotechnology. Mesoporous silica nanoparticles (MSNs) are investigated improve aspects attributed advantageous structural features this nanomaterial. MSNs engineered alter their properties size, shape, porosity, surface functionality, adjuvanticity. This review explores immunological use vehicles for immune‐adjuvants, (APCs). The also details current remodel tumor microenvironment positively reciprocate toward anti‐tumor in combination with other therapies photodynamic/thermal therapeutic effect cancer. Last, present demands future scenarios discussed.
Язык: Английский
Процитировано
13
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Окт. 2, 2024
The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. agonists have shown potential enhancing immune responses, particularly tumors resistant to traditional therapies. This scholarly review examines the diverse categories agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, delivery methods remain obstacles broader use. Ongoing research innovation are essential overcoming hurdles. could play transformative role treatment, patients with hard-to-treat malignancies, by harnessing body's system eliminate cells.
Язык: Английский
Процитировано
13
Biomaterials, Год журнала: 2024, Номер 313, С. 122766 - 122766
Опубликована: Авг. 22, 2024
Язык: Английский
Процитировано
9
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Фев. 11, 2025
Background STING is a core signaling hub molecule in the innate immune system, involved various diseases, including infectious autoimmune tumors, aging, organ fibrosis, and neurodegenerative diseases. Its activation has shown great potential anti-tumor anti-infective therapies, with agonists emerging as promising approach cancer immunotherapy recent years. This study identifies research trends directions field by collecting analyzing relevant literature. Methods A total of 527 publications regarding 107 about inhibitors were retrieved from WOS Core Collection database. Bibliometric information was extracted CiteSpace VOSviewer software for visualization. Results It shows that on both burgeoning rapidly. The United States China are leading contributors this field. Application primarily focuses immunotherapy, while target inflammation, particularly neuroinflammation acute lung injury. Conclusion Current emphasizes optimizing permeability, efficacy, safety, nanotechnology lipid nanoparticles being prominent delivery techniques. Future expected to focus drug development clinical applications. comprehensive bibliometric analysis provides insights guide further investigation agonist/inhibitor.
Язык: Английский
Процитировано
2
Future Oncology, Год журнала: 2025, Номер 21(2), С. 195 - 200
Опубликована: Янв. 14, 2025
BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, combination 1703880 an anti-programmed cell protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating plus ezabenlimab patients with advanced solid tumors. The utilizes innovative lead-in design; all receive monotherapy Cycle therapy from 2. primary endpoint dose-limiting toxicities during the maximum tolerated dose evaluation period. Results will inform future development for treatment metastatic or recurrent malignancies.Clinical Trial number: NCT05471856.
Язык: Английский
Процитировано
1
ACS Nano, Год журнала: 2025, Номер unknown
Опубликована: Март 2, 2025
We demonstrate reprogramming of the tolerogenic immune environment in liver for mounting an effective response against often-fatal pancreatic cancer metastases. This was achieved by engineering a lipid nanoparticle (LNP) to deliver mRNA encoding KRAS G12D neoantigenic epitope along with cGAMP, dinucleotide agonist stimulator interferon genes (STING) pathway, capable activating type I response. cGAMP/mKRAS/LNP were synthesized microfluidics approach involving nanoprecipitation and cGAMP ionizable lipid, MC3. Controls included nanoparticles delivering individual components or wild-type RAS sequence. The dual delivery carrier successfully activated pathway vitro as well vivo, costimulatory receptor (CD80 CD86) MHC-I expression on antigen-presenting cells (APC). allowed generation IFN-γ producing cytotoxic T cells, metastatic (KPC) mouse model. Noteworthy, intravenous injection suppressed growth significantly prolonged animal survival, both prophylactically during treatment established protective mediated perforin-releasing CD8+ engaged cell killing. Importantly, could also be adoptively transferred injecting splenocytes (containing memory cells) from treated into nontreated recipient mice. study demonstrates that immune-protective niche can STING mutant via LNPs, offering prophylactic therapeutic advantages.
Язык: Английский
Процитировано
1
Cancers, Год журнала: 2024, Номер 16(13), С. 2425 - 2425
Опубликована: Июнь 30, 2024
Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression cancer cells is less well characterized, but agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for by immunohistochemistry. STING-positive were found 130 (93.5%) entities. The highest positivity rates occurred squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%–95.7%); adenocarcinoma pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); serous high-grade ovarian (86.0%). High linked adverse phenotypes breast cancer, clear renal carcinoma, colorectal adenocarcinoma, hepatocellular papillary carcinoma thyroid (p < 0.05). In pTa urothelial carcinomas, associated with low-grade = 0.0002). Across all tumors, paralleled PD-L1 0.0001 each) unrelated density CD8+ lymphocytes. variable across may be related aggressive phenotype positivity. lack relationship tumor-infiltrating lymphocytes argues against a significant IFN production positive
Язык: Английский
Процитировано
7