ArticleCancers2026
In Vitro Characterization of Internalization Pathways and Cytotoxic Activity of Anti-HSPG2 Antibody-Drug Conjugates in MDA-MB-231-LM2 Cells.
Article in Cancers, 2026. 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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5 authors.
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Abstract
BACKGROUND/
objectivesThis study presents a mechanistic assessment of an anti-HSPG2 monoclonal antibody (AM6) as an antibody-drug conjugate (ADC) carrier in vitro.
methodsUsing live-cell confocal imaging with pathway inhibitors, we qualitatively characterized AM6 internalization and trafficking and compared linker/payload configurations for intracellular delivery and in vitro cytotoxicity.
resultsAM6 exhibited rapid cellular entry in MDA-MB-231-LM2 cells, with contributions from clathrin-mediated endocytosis and macropinocytosis, followed by accumulation in endo-lysosomal compartments. Consistent with these trafficking observations, AM6 ADCs bearing cleavable linkers and a potent payload (MMAE) produced more pronounced antiproliferative effects in MDA-MB-231-LM2 and other HSPG2-positive tumor cells than non-cleavable constructs, whereas doxorubicin-based ADCs showed limited activity and greater aggregation risk.
conclusionsOverall, the data inform linker/payload selection and highlight considerations for future work, including quantitative internalization, antigen-negative or knockdown controls, and in vivo pharmacology.
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