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Liposomal Irinotecan: A Review as First-Line Therapy in Metastatic Pancreatic Adenocarcinoma.

Drugs

January 2025

Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.

Liposomal irinotecan (Onivyde), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

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A successful therapeutic outcome in the treatment of solid tumours requires efficient intratumoural drug accumulation and retention. Here we demonstrate that zinc gluconate in oral supplements assembles with plasma proteins to form ZnO nanoparticles that selectively accumulate into papillary Caki-2 renal tumours and promote the recruitment of dendritic cells and cytotoxic CD8 T cells to tumour tissues. Renal tumour targeting is mediated by the preferential binding of zinc ions to metallothionein-1X proteins, which are constitutively overexpressed in Caki-2 renal tumour cells.

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Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

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Background: Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora (Franch.).

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A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.

J Transl Med

January 2025

Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.

Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.

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