Abstract
Triple-negative breast cancers (TNBCs) are heterogeneous and metastatic, and targeted therapy is highly needed for TNBC treatment. Recent studies showed that extracellular vesicles (EV) have great potential to deliver therapies to treat cancers. This study aimed to develop and evaluate a natural compound, verrucarin A (Ver-A), delivered by targeted EV, to treat TNBC. First, the surface expression of epidermal growth factor receptor (EGFR) and CD47 were confirmed with immunohistochemistry (IHC) staining of patient tissue microarray, flow cytometry and Western blotting. EVs were isolated from HEK 293F culture and surface tagged with anti-EGFR/CD47 mAbs to construct mAb-EV. The flow cytometry, confocal imaging and live-animal In Vivo Imaging System (IVIS) demonstrated that mAb-EV could effectively target TNBC and deliver the drug. The drug Ver-A, with dosage-dependent high cytotoxicity to TNBC cells, was packed in mAb-EV. The anti-TNBC efficacy study showed that Ver-A blocked tumor growth in both 4T1 xenografted immunocompetent mouse models and TNBC patient-derived xenograft models with minimal side effects. This study demonstrated that the targeted mAb-EV-Ver-A had great potential to treat TNBCs.
Highlights
Triple-negative breast cancers (TNBCs) are HER2− /ER− /PR− and highly aggressive, metastatic, and heterogeneous [1,2,3]
The results demonstrated that monoclonal antibody (mAb)-extracellular vesicles (EV)-verrucarin A (Ver-A) had great potential to target and treat TNBCs
The anti-tumor efficacy was confirmed in both mouse TNBC xenograft immunocompetent models and in a patientderived xenograft (PDX) model
Summary
Triple-negative breast cancers (TNBCs) are HER2− /ER− /PR− and highly aggressive, metastatic, and heterogeneous (five subtypes, revised algorithm TNBCtype-IM) [1,2,3]. The antibody-drug conjugate, Sacituzumab Govitecan, has been approved to treat trophoblast cell-surface antigen 2 (Trop-2)+ TNBC [11,12,13,14,15]. The success of these therapeutics demonstrated that targeted therapy or therapeutic combination has great potential to treat TNBCs. Considering the challenges of early metastases and relapses [16], heterogeneity of TNBCs, new targeted therapies are highly desired
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
