Publications by authors named "Timothee David"
A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer.
J Immunother Cancer
January 2024
Article Synopsis
- Triple-negative breast cancer (TNBC) has a poor prognosis, and cathepsin D (cath-D) is a key target for antibody therapies to enhance natural killer (NK) cell activity against tumors.
- This study explored the effectiveness of engineered anti-cath-D antibodies in triggering NK cell-mediated attacks (ADCC) and their potential in combination therapies for TNBC.
- Results showed that the Fc-engineered antibodies activated NK cells and promoted ADCC against TNBC cells, suggesting their promise as a treatment strategy when used alongside other therapies.
Background And Purpose: Triple-negative breast cancer (TNBC) has poorer outcomes than other breast cancers (BC), including HER2 BC. Cathepsin D (CathD) is a poor prognosis marker overproduced by BC cells, hypersecreted in the tumour microenvironment with tumour-promoting activity. Here, we characterized the immunomodulatory activity of the anti-CathD antibody F1 and its improved Fab-aglycosylated version (F1M1) in immunocompetent mouse models of TNBC (C57BL/6 mice harbouring E0771 cell grafts) and HER2-amplified BC (BALB/c mice harbouring TUBO cell grafts).
View Article and Find Full Text PDFAlternative therapeutic strategies based on tumor-specific molecular targets are urgently needed for triple-negative breast cancer (TNBC). The protease cathepsin D (cath-D) is a marker of poor prognosis in TNBC and a tumor-specific extracellular target for antibody-based therapy. The identification of cath-D substrates is crucial for the mechanistic understanding of its role in the TNBC microenvironment and future therapeutic developments.
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