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journal article·2025-01Open access

Sustained Endocytosis Inhibition via Locally‐Injected Drug‐Eluting Hydrogel Improves ADCC‐Mediated Antibody Therapy in Colorectal Cancer

Chong Wu, Xiaoting Liu, Rong Liu, Shiyao Song, Zi‐Fan Zheng, Yilin Zeng, Yong Mei, Jing‐Yang Zhang, Qijia Duan, Run Lin, Jin‐Zhi Du, Weiling He

Advanced Science· Volume 12· Issue 2
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Source abstract

Abstract

Abstract 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.
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Research context

Polymers

OpenAlex topics: Monoclonal and Polyclonal Antibodies Research · Multiple Myeloma Research and Treatments · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong 510080 China

Department of Immunology Zhongshan School of Medicine Sun Yat‐sen University Guangzhou Guangdong 510080 China

School of Medicine South China University of Technology Guangzhou Guangdong 510006 China

Guangdong Institute for Drug Control NMPA Key Laboratory of Quality Control and Evaluation of Pharmaceutical Excipient Guangzhou 510663 China

Department of Pediatrics, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong 510080 China

Department of Radiology, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong 510080 China

School of Biomedical Sciences and Engineering, Guangzhou International Campus South China University of Technology Guangzhou Guangdong 511442 China

National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology Guangzhou Guangdong 510006 China

Department of Gastrointestinal Surgery Xiang'an Hospital of Xiamen University, School of Medicine Xiamen University Xiamen Fujian 361000 China

Funding

National Natural Science Foundation of China

References (47)

Show source-provided references
1. 10.1016/j.ccr.2014.02.02510.1016/j.ccr.2014.02.025 ↗
2. 10.1016/S2468-1253(19)30345-010.1016/S2468-1253(19)30345-0 ↗
3. 10.1056/NEJMoa080501910.1056/NEJMoa0805019 ↗
4. 10.1016/S1470-2045(14)70118-410.1016/S1470-2045(14)70118-4 ↗
5. 10.1093/annonc/mdq63210.1093/annonc/mdq632 ↗
6. 10.1056/NEJMra070770410.1056/NEJMra0707704 ↗
7. 10.1007/s00109-014-1161-210.1007/s00109-014-1161-2 ↗
8. 10.1158/2159-8290.CD-14-046210.1158/2159-8290.CD-14-0462 ↗
9. 10.1245/s10434-017-6264-x10.1245/s10434-017-6264-x ↗
10. 10.1002/cncr.2780410.1002/cncr.27804 ↗
11. 10.1126/scisignal.aaw828810.1126/scisignal.aaw8288 ↗
12. 10.1038/nrc252110.1038/nrc2521 ↗
13. 10.1038/nrc323610.1038/nrc3236 ↗
14. 10.1038/nrc191310.1038/nrc1913 ↗
15. 10.1038/s41568-023-00574-610.1038/s41568-023-00574-6 ↗
16. 10.1038/7470410.1038/74704 ↗
17. 10.1038/s41467-018-07608-w10.1038/s41467-018-07608-w ↗
18. 10.1038/s41467-022-30142-910.1038/s41467-022-30142-9 ↗
19. 10.1002/anie.20230477910.1002/anie.202304779 ↗
20. 10.1016/j.ccell.2015.03.00510.1016/j.ccell.2015.03.005 ↗
21. 10.1016/j.cell.2020.02.01910.1016/j.cell.2020.02.019 ↗
22. 10.1101/cshperspect.a01694910.1101/cshperspect.a016949 ↗
23. 10.1016/j.jid.2018.06.19010.1016/j.jid.2018.06.190 ↗
24. a)A. C. Trials australianclinicaltrials.gov.au https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619001051134 accessed;
25. b)australianclinicaltrials.gov.au https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619001527156 accessed.
26. 10.1016/j.jconrel.2019.01.02610.1016/j.jconrel.2019.01.026 ↗
27. 10.1038/4221810.1038/42218 ↗
28. 10.1126/scitranslmed.abc780410.1126/scitranslmed.abc7804 ↗
29. 10.1158/1078-0432.CCR-08-281310.1158/1078-0432.CCR-08-2813 ↗
30. 10.1016/j.annonc.2019.10.00710.1016/j.annonc.2019.10.007 ↗
31. 10.1093/annonc/mdr62310.1093/annonc/mdr623 ↗
32. 10.1016/j.ccr.2014.05.01910.1016/j.ccr.2014.05.019 ↗
33. 10.1158/2159-8290.CD-17-100910.1158/2159-8290.CD-17-1009 ↗
34. 10.1158/1078-0432.CCR-09-077310.1158/1078-0432.CCR-09-0773 ↗
35. 10.1038/ncomms1366510.1038/ncomms13665 ↗
36. 10.1038/onc.2009.23410.1038/onc.2009.234 ↗
37. 10.1126/sciadv.aax557610.1126/sciadv.aax5576 ↗
38. 10.1111/tra.1227210.1111/tra.12272 ↗
39. 10.1038/s41467-022-30142-910.1038/s41467-022-30142-9 ↗
40. Banushi B. · Nat. Rev. Cancer · 2023
41. 10.1002/smll.20210477310.1002/smll.202104773 ↗
42. 10.1093/annonc/mdw23510.1093/annonc/mdw235 ↗
43. 10.6004/jnccn.2021.001210.6004/jnccn.2021.0012 ↗
44. 10.1126/scitranslmed.abm368710.1126/scitranslmed.abm3687 ↗
45. 10.1126/scitranslmed.aax831310.1126/scitranslmed.aax8313 ↗
46. 10.15252/embr.20215412810.15252/embr.202154128 ↗
47. 10.1016/j.bioactmat.2023.10.00310.1016/j.bioactmat.2023.10.003 ↗