P1, N=4, Terminated, University of Calgary | N=56 --> 4 | Trial completion date: Dec 2024 --> Jul 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Jul 2025; Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.

Patients with abnormal renal function, BRCA1 mutations, or those at high risk of developing skeletal-related events may benefit from denosumab over zoledronic acid. During denosumab treatment in patients with renal dysfunction, attention should be paid to the occurrence of hypocalcemia.

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.

The patient was started on a low phosphate diet, sevelamer, and acetazolamide and was instructed to avoid calcium and vitamin D supplements. Intravenous Zoledronic Acid was also given. The patient reported improvement in his symptoms in the follow-up visits.

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.

LC-MS showed that 6-FM-treated CHO-K1 cells accumulated substantial MPP while risedronate, an inhibitor of farnesyl diphosphate synthase, primarily increased DMAPP/IPP...Both BTN2A1 + BTN3A3-transfected CHO-K1 cells and BTN3A1 knockout K562 cells could detect 6-FM, despite their absence of BTN3A1. Our findings provide evidence that MPP functions as a natural ligand of BTN3A3 and establish a foundation for elucidating biological functions of BTN3A3 complementary to the established BTN3A1 pathway.

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.

Drug sensitivity analysis demonstrated a correlation between LGALS1 expression and the response to agents such as zoledronate and staurosporine. Immune- and lipid metabolism-related genes contribute to macrophage polarization and are closely linked to GBM prognosis. The identified gene signature provides prognostic value and potential therapeutic targets for immunometabolic modulation in GBM.

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.

We specifically engineer these CAFs in situ to enhance antitumor immunity using an innovative nanodrug, IL-15 plasmid-loaded FAP-sensitive MgCa/z-Gly-Pro-pamidronate acid nanoparticles (PN/MCG NPs)...Furthermore, we also prove that FAP+ αSMA+ human mammary fibroblast cells (FAP+ αSMA+ HMFs) also can be engineered by PN/MCG NPs in vitro. Our findings demonstrate that in situ CAF engineering is a promising strategy to remodel the tumor microenvironment and enhance immunotherapy in TNBC.

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.

Recent advances in γδ T cell-based immunotherapies, particularly in combination with agents such as zoledronate bisphosphonate that enhances tumor recognition, show promising preclinical results. However, obstacles such as the suppressive tumor microenvironment and immune evasion mechanisms remain significant. This chapter highlights the therapeutic potential of γδ T cells in prostate cancer and the need for further research to optimize these approaches.