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DRUG:

clodronate disodium

Company:
Generic mfg.
Drug class:
Bone resorption factor inhibitor
1m
Experimental study of tumor-associated macrophage-derived SPP1 inhibit CD8+ T cells to promote Colorectal cancer progression. (PubMed, Neoplasia)
In a macrophage-depleted murine CRC model established with clodronate (CL2MDP) liposomes and MC38 cells, macrophage depletion significantly inhibited tumor growth, accompanied by reduced SPP1 expression and increased infiltration of CD8⁺ T cells and type 1 cytotoxic T (Tc1) cells...These effects were attenuated by SPP1 neutralization or CD44 inhibition. Collectively, these findings elucidated TAM-derived SPP1 as a key mediator of immune suppression in CRC and suggested that the TAM-SPP1 axis is a potential therapeutic target.
Journal
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • SPP1 (Secreted Phosphoprotein 1)
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clodronate disodium
1m
High-dimensional phenotyping reveals novel macrophage-like and hybrid subsets within murine splenic conventional dendritic cells. (PubMed, PLoS One)
This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11chighMHCIIhigh cDCs in C57BL/6 mice...These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets.
Preclinical • Journal
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MERTK (MER Proto-Oncogene, Tyrosine Kinase) • CD4 (CD4 Molecule) • CCR2 (C-C Motif Chemokine Receptor 2) • CDK1 (Cyclin-dependent kinase 1) • ITGAX (Integrin Subunit Alpha X) • CX3CR1 (C-X3-C Motif Chemokine Receptor 1)
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clodronate disodium
2ms
Oridonin Ameliorates Macrophage Oxidative Stress and Pyroptosis In Liver Ischemia-Reperfusion Injury by Inhibiting Mitochondrial ROS/TXNIP/NLRP3. (PubMed, Shock)
Oridonin effectively protects against LIRI by decreasing macrophage M1 polarization, oxidative stress, and pyroptosis through inhibition of the mitochondrial ROS/TXNIP/NLRP3 pathway.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL18 (Interleukin 18) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3) • TXNIP (Thioredoxin Interacting Protein) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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clodronate disodium
3ms
Engineering and evaluation of precision-glycosylated clickable albumin nanoplatform for targeting the tumor microenvironment. (PubMed, Theranostics)
Clodronate-loaded glycosylated albumins were tested for tumor-associated macrophage (TAM) depletion...Integrating PET with ST provides a robust framework for mechanistic mapping of nanomedicine uptake. The CAN-DGIT platform offers a versatile strategy for developing targeted theranostic agents with immunomodulatory potential.
Journal
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MRC1 (Mannose Receptor C-Type 1) • SLC2A1 (Solute Carrier Family 2 Member 1)
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clodronate disodium
3ms
Single-cell multiomics reveals macrophage-derived IL-23 and CXCL9/10 drive pathogenic IFNG+IL17+ T cells in immunotherapy-related colitis. (PubMed, J Immunother Cancer)
IFNG+IL17+CD4+ T cells and CXCL9/10-producing macrophages are key mediators of irColitis. Targeting IL-23 signaling and intestinal macrophages represents a promising strategy to alleviate gut immunopathology without compromising the efficacy of ICB therapy.
Journal
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IFNG (Interferon, gamma) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CD4 (CD4 Molecule) • IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha) • CXCR3 (C-X-C Motif Chemokine Receptor 3)
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clodronate disodium
4ms
TAMs-mediated resistance to oncolytic virus M1 in solid tumors. (PubMed, J Immunother Cancer)
TAMs, particularly M1-like subsets, play a critical role in mediating resistance to OVM therapy by reducing viral persistence and suppressing CD8+ T-cell responses. Targeting TAMs significantly improves the antitumor efficacy of OVM in solid tumors. These findings support the development of TAMs-targeted combination strategies to optimize oncolytic virotherapy.
Journal
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CD8 (cluster of differentiation 8) • CSF1R (Colony stimulating factor 1 receptor) • GZMB (Granzyme B)
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clodronate disodium
4ms
RIPK3 Protects Against Endothelial Activation and Vascular Permeability in a Mouse Model of Ischemia-Reperfusion Injury. (PubMed, Arterioscler Thromb Vasc Biol)
Clodronate liposomes were used to reduce circulating monocytes in vivo...Endothelial RIPK3 suppresses EC activation and inflammation associated with IL-6 and VCAM-1 elevation to protect the vascular barrier in the context of intestinal I/R injury. Thus, endothelial RIPK3 plays surprisingly beneficial roles that reduce I/R injury-induced vascular dysfunction.
Preclinical • Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • VCAM1 (Vascular Cell Adhesion Molecule 1)
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clodronate disodium
4ms
Glutamine synthetase loss in β-catenin-mutant hepatocellular carcinoma promotes tumor burden through macrophage metabolic reprogramming. (PubMed, Hepatology)
We demonstrate unique metabolic dependency of β-catenin-mutated HCCs on GS in tumor cells which is diverted to macrophages upon GS elimination in tumor cells. This adaptation alters macrophage metabolism and function leading to compromised immunosurveillance and greater tumor burden. Our study reveals a metabolic dynamic between HCC cells and macrophages with impact on tumor biology.
Journal
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GLUL (Glutamate-Ammonia Ligase)
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NFE2L2 mutation
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clodronate disodium
5ms
B7-H4 ImmunoPET Imaging Tracks Tumor-Associated Macrophage Changes in Prostate Cancer. (PubMed, Mol Pharm)
To distinguish PET signals from tumor cells versus macrophages, immunocompetent C57BL/6 mice bearing syngeneic TRAMP-C2 prostate tumors were divided into three cohorts and treated with PBS (control), cold anti-B7-H4 mAb (for B7-H4 blockade), or clodronate liposome (for macrophage depletion)...Collectively, these results show that [89Zr]Zr-DFO-2H9 binds B7-H4 with high affinity and specificity and reflects changes in TAM levels in vivo. The new radiotracer shows promise for detecting B7-H4 positive tumors and TAM levels, profiling the immune microenvironment, and monitoring macrophage-targeted immunotherapies.
Journal • IO biomarker
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VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
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clodronate disodium
6ms
Liposomal 188Rhenium Plus Macrophage Depletion Enhances Anti-PD-L1 Efficacy and B Cell Infiltration Against Lung Metastatic Cancer. (PubMed, Cancer Sci)
A lung metastatic colon cancer model was established via intravenous injection of CT26-luciferase cells and then treated with Lipo-Re188 (11.1 MBq, 30% of MTD), liposomal clodronate (Lipo-clod) for macrophage depletion, and/or anti-PD-L1 antibody...Our study reveals that triple therapy overcomes immunosuppressive feedback and promotes a tumor-suppressive microenvironment. These findings support a rational combination strategy integrating radiopharmaceutical therapy with immune modulation for metastatic cancer treatment.
Journal
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CSF2 (Colony stimulating factor 2)
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clodronate disodium
6ms
Icariside II ameliorates slow transit constipation by inhibiting macrophage polarization and suppressing the cGAS-STING pathway. (PubMed, Eur J Pharmacol)
This study provides evidence that ICS II exerts significant anti-inflammatory and neuroprotective effects. This is achieved by inhibiting the cGAS-STING pathway and suppressing macrophage M1 polarization, suggesting its potential as a therapeutic agent for STC.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • STING (stimulator of interferon response cGAMP interactor 1)
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clodronate disodium • loperamide
6ms
Combination Therapy: Hyperbaric Oxygen and PENTOCLO for Treatment of Osteoradionecrosis of the Mandible (clinicaltrials.gov)
P3, N=24, Recruiting, Sunnybrook Health Sciences Centre | Not yet recruiting --> Recruiting | Trial completion date: Nov 2025 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2027
Enrollment open • Trial completion date • Trial primary completion date
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clodronate disodium