Benjamin E. Blass

Background/objectives: This study presents a mechanistic assessment of an anti-HSPG2 monoclonal antibody (AM6) as an antibody–drug conjugate (ADC) carrier in vitro. Methods: Using 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. Results: AM6 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. Conclusions: Overall, the data inform linker/payload selection and highlight considerations for future work, including quantitative internalization, antigen-negative or knockdown controls, and in vivo pharmacology.

Vision loss is one of the most debilitating eye impairments, with the leading causes such as cataracts, glaucoma, injuries to the surface of the eye and ag

Invasive candidiasis remains a significant health concern, as it is associated with a high mortality risk. In addition, the risk of infection is significantly elevated in immunocompromised patients such as those with HIV, cancer, or those taking imcmunosuppressive drugs as a result of organ transplantation. The majority of these cases are caused by C. albicans, and C. glabrata is the second most common cause. These infections are typically treated using approved antifungal agents, but the rise of drug-resistant fungi is a serious concern. As part of our on-going effort to identify novel antifungal agents, we have studied the in vitro antifungal properties of a series of sulfonamide analogs of (2S, 4R)-Ketoconazole. Herein we report on the in vitro activity against the key fungal pathogens C. albicans, and C. glabrata.

Selective action of γ-butyrolactones and oxazolidinones towards σ ₂ receptor.