O-P04 Sonodynamic Therapy Complements PD-L1 Immune Checkpoint Inhibition in a Murine Model of Pancreatic Cancer
نویسندگان
چکیده
Abstract Background The emergence of immune checkpoint inhibitors (ICI’s) in the past decade has proven transformative area immuno-oncology. PD-1 / PD-L1 axis been particularly well studied and monoclonal antibodies developed to block either receptor (anti PD-1) or its associated ligand PD-L1) can generate potent anti-tumour immunity certain tumour models. However, many “immune cold” tumours remain unresponsive ICI’s. Sonodynamic therapy (SDT) is a targeted anti-cancer treatment that uses ultrasound activate sensitiser with resulting generation reactive oxygen species (ROS) causing direct cell death. SDT also shown stimulate adaptive system pre-clinical cancer model. We investigate ability combining ICI microbubble mediated at controlling growth bilateral pancreatic Methods Preparation O2MB-RB are below (scheme 1). Cytotoxicity immunotherapy in-vivo illustrated (Figure Figure 1 highlights T110299 cells were subcutaneously implanted right left dorsum C57 mice. Group received an IP injection anti-mouse antibody (10mg/kg). After 2 hours, mice this group IV suspension while receiving applied right-hand-side (target) tumour. same as but no anti antibody; 3 anti-PD-L1 alone 4 remained untreated. Flow cytometry analysis carried out infiltrating CD4+ CD8+ T-lymphocytes. Results results demonstrated significant 287% decrease volume when compared untreated animals 11 days following initial SDT, which reduced further 369% was combined treatment. Analysis residual tissues remaining after revealed increased levels T-lymphocytes (respectively 4.65 3.16-fold more) off-target where target treated anti-PD-L1, tumours. These suggest elicits response potentiated by particular model cancer. Conclusions In conclusion, cancer, enables control both enhanced Combining treatment, tolerated, could provide attractive option for patients advanced disease who may not be physically capable undertaking toxic chemotherapy regimen.
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ژورنال
عنوان ژورنال: British Journal of Surgery
سال: 2021
ISSN: ['1365-2168', '0007-1323']
DOI: https://doi.org/10.1093/bjs/znab429.045