However, conventional ex vivo expansion protocols using zoledronic acid (Zol) and IL-2 often lead to terminal differentiation and diminished effector function. In orthotopic tumor models, γδ2 T-Da cells enhanced tumor control, reduced TNBC metastasis, and prolonged survival of GBM-bearing mice. These results suggest that dasatinib improves γδ T cell yield and function, providing a practical and translatable strategy for optimizing γδ T cell-based adoptive therapy, particularly for solid tumors.Trial registration: Trial number: CMUH111-REC3-185.

The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy...Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.

Simulated treatment of bone-adapted tumors with the bisphosphonate zoledronic acid stabilizes bone density but has limited or highly variable effects on tumor growth. These results suggest that OC inhibition alone may be insufficient to restrain tumor expansion once tumors have adapted to the bone microenvironment. Together, these findings support the hypothesis that tumor adaptation to the bone microenvironment governs dependence on bone-derived growth factors and response to OC-targeted therapy, underscoring the value of mechanistic modeling for elucidating tumor-bone interactions and guiding tumor-type-specific treatment strategies for TIBD.

In this study, we evaluated the impact of human serum on the expansion, phenotype, function, and transcriptomic landscape of Vγ9Vδ2 γδ T cells cultured with zoledronate and cytokines under serum-free versus serum-containing conditions...Furthermore, re-exposure to serum late in culture had minimal influence on γδ T cell functionality. These findings demonstrate the feasibility and advantages of serum-free expansion protocols for Vγ9Vδ2 γδ T cells, offering improved consistency, safety, and therapeutic potential.

Notably, zoledronate-expanded Vγ9Vδ2 γδ T-cell lines achieved cytotoxicity comparable to PHA-expanded αβ cells. Together, these in vitro data reveal subset-specific BLN responses and support the hypothesis that ex vivo-expanded Vγ9Vδ2 γδ T cells could complement BLN-mediated cytotoxicity, particularly under conditions of higher CD19 density and lower target burden. These findings provide a mechanistic framework for future testing of γδ T-cell/BLN combination strategies in patient-derived models and clinical studies.

Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11-ERLIN1 interaction and restoring cholesterol homeostasis. ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11-ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

P=N/A, N=0, Withdrawn, University Hospital, Rouen | N=72 --> 0 | Not yet recruiting --> Withdrawn

Pamidronate (APD), a nitrogen-containing bisphosphonate, has shown potential in managing osteolytic lesions by inhibiting osteoclast activity...Moreover, CHA exhibited excellent biocompatibility with no observed systemic toxicity. These results underscore the promise of CHA as a clinically translatable therapeutic strategy for the treatment of osteolytic bone metastases.

Computed tomography confirmed mixed calcifications (26×24 mm) with heterogeneous enhancement. Magnetic resonance imaging revealed an ovoid calcified soft-tissue mass within the soleus/paratibial region, marked surrounding edema, and mild periosteal reaction, supporting an intermediate-stage juxtacortical MO and making a primary bone tumor unlikely. Management included nonsteroidal anti-inflammatory drugs, ketoprofen, then indomethacin, zoledronic acid infusion, and physical therapy emphasizing pain-free mobilization and ultrasound therapy.

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.

He was treated with intravenous fluids, zoledronic acid, and calcitonin with symptomatic improvement and was referred to a tertiary center for surgical evaluation...Instead, a broad differential should be maintained, including concurrent malignancy or inherited syndromes. Early recognition of overlapping etiologies is essential to prevent delayed diagnosis or missed malignancy in patients with persistent hypercalcemia.

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.