ArticleCancer science2025
Liposomal
Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Radionuclides such as Rhenium-188 (Re188) hold promise for treating metastatic cancers due to their cytotoxic effects and potential to stimulate systemic anti-tumor immunity. However, mononuclear phagocyte system-mediated clearance of liposome encapsulated Re188 (Lipo-Re188) limits its tumor delivery. This study aimed to enhance the therapeutic effect of Lipo-Re188 against lung metastases through macrophage depletion and immune checkpoint blockade. 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. Tumor progression was monitored by bioluminescence imaging, and radionuclide biodistribution was assessed at 1, 24, and 48 h post-injection. Flow cytometry was used to assess immune cell populations in the spleen and tumor microenvironment (TME). Cytokine levels were measured using a bead-based multiplex assay and analyzed by flow cytometry. Macrophage depletion significantly enhanced tumor accumulation of Lipo-Re188 while reducing hepatic uptake and prolonging survival. The combination of Lipo-clod and Lipo-Re188 promoted B cells, restored functional T cells, and suppressed MDSC in both spleen and TME. Notably, IL-1α and GM-CSF levels were significantly elevated in the combination group. Triple therapy with Lipo-clod, Lipo-Re188, and anti-PD-L1 provided the greatest survival benefit, highest intratumoral B cell accumulation, and lowest interstitial macrophage levels, with no significant biological toxicity. 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.
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