biostudies-literatureDesroys du Roure PLigue Régionale de l’HeraultRégion Occitanie Pyrénées-MéditerranéeLigue Régionale de la Charente MaritimeAgence Nationale de la RechercheInserm TransfertUniversité de MontpellierLigue Régionale du Garde007135https://www.ebi.ac.uk/biostudies/studies/S-EPMC10828871biostudies-literatureUnknown12(1)<h4>Introduction</h4>Triple-negative breast cancer (TNBC) prognosis is poor. Immunotherapies to enhance the antibody-induced natural killer (NK) cell antitumor activity are emerging for TNBC that is frequently immunogenic. The aspartic protease cathepsin D (cath-D), a tumor cell-associated extracellular protein with protumor activity and a poor prognosis marker in TNBC, is a prime target for antibody-based therapy to induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). This study investigated whether Fc-engineered anti-cath-D antibodies trigger ADCC, their impact on antitumor efficacy and tumor-infiltrating NK cells, and their relevance for combinatory therapy in TNBC.<h4>Methods</h4>Cath-D expression and localization in TNBC samples were evaluated by western blotting, Journal for immunotherapy of cancerA 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.PMC10828871N/ALabEx MabImprove ANR-10-LABX-53-01Mallavialle ARoger PChateau MCLajoie LNgo GGuiu SChardes TVillalba MDesroys du Roure PGarambois VRubio LFenou LJarlier MMartineau PBoissiere-Michot FDavid TAlcaraz LBGros LLiaudet-Coopman EMansouri HCoenon LLaurent-Matha VfalseA 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.<h4>Introduction</h4>Triple-negative breast cancer (TNBC) prognosis is poor. Immunotherapies to enhance the antibody-induced natural killer (NK) cell antitumor activity are emerging for TNBC that is frequently immunogenic. The aspartic protease cathepsin D (cath-D), a tumor cell-associated extracellular protein with protumor activity and a poor prognosis marker in TNBC, is a prime target for antibody-based therapy to induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). This study investigated whether Fc-engineered anti-cath-D antibodies trigger ADCC, their impact on antitumor efficacy and tumor-infiltrating NK cells, and their relevance for combinatory therapy in TNBC.<h4>Methods</h4>Cath-D expression and localization in TNBC samples were evaluated by western blotting, 2024-01-01T00:00:00Z2024 Jan2026-07-14T21:00:13.192Z2026-06-24T03:06:49.28ZS-EPMC108288713829076810.1136/jitc-2023-007135