Asset Details
Do you wish to reserve the book?
Sustained Endocytosis Inhibition via Locally‐Injected Drug‐Eluting Hydrogel Improves ADCC‐Mediated Antibody Therapy in Colorectal Cancer
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Sustained Endocytosis Inhibition via Locally‐Injected Drug‐Eluting Hydrogel Improves ADCC‐Mediated Antibody Therapy in Colorectal Cancer
Do you wish to request the book?
Sustained Endocytosis Inhibition via Locally‐Injected Drug‐Eluting Hydrogel Improves ADCC‐Mediated Antibody Therapy in Colorectal Cancer
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Sustained Endocytosis Inhibition via Locally‐Injected Drug‐Eluting Hydrogel Improves ADCC‐Mediated Antibody Therapy in Colorectal Cancer
2025
Overview
The epidermal growth factor receptor (EGFR) is a validated therapeutic target for RAS/RAF wild‐type colorectal cancer (CRC). However, monoclonal antibody‐based anti‐EGFR therapies such as cetuximab have limited effectiveness. Herein, it is identified that EGFR internalization is associated with poor treatment response and prognosis in patients with CRC, based on a retrospective analysis of patients treated with cetuximab. It is further demonstrated that the endocytosis inhibitor prochlorperazine (PCZ) can move EGFR, which is hidden inside the cell, to the cell surface to improve therapeutic antibody binding. Thus, a thermosensitive hydrogel co‐loaded with cetuximab and PCZ (Gel@Cmab/PCZ) is constructed for sustained inhibition of endocytosis and effective cetuximab delivery. Peritumoral injection of Gel@Cmab/PCZ shows strong antitumor efficacy in subcutaneous and orthotopic CRC tumor models and completely abrogated liver metastasis when combined with chemotherapy. In a humanized patient‐derived xenograft model, a single injection of Gel@Cmab/PCZ with one‐third of the conventional cetuximab dose achieved 91% tumor growth inhibition, which promoted NK cell infiltration into tumor tissues and their antibody‐dependent cell‐mediated cytotoxicity effect. This study represents a novel strategy to boost the monoclonal antibody‐mediated anti‐tumor response in CRC. In this study, a thermosensitive hydrogel loaded with cetuximab and endocytosis inhibitor prochlorperazine is designed to enhance the therapeutic efficacy of colorectal cancer. The hydrogel can sustainably release prochlorperazine at the tumor site, which led to the increased expression of EGFR on the cell membrane, and thus enhances antibody‐dependent cell‐mediated cytotoxicity of cetuximab. This strategy boosts antibody‐mediated anti‐tumor response in multiple tumor models.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Antibody-Dependent Cell Cytotoxicity - drug effects
/ antibody‐dependent cell‐mediated cytotoxicity
/ Antineoplastic Agents, Immunological - pharmacology
/ Cells
/ Cetuximab - administration & dosage
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - metabolism
/ epidermal growth factor receptor
/ Female
/ Humans
/ hydrogel
/ Male
/ Mice
/ Patients
/ Proteins
