HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies.

Abstract
Polyethylene glycol (PEG) is attached to many peptides, proteins, liposomes, and nanoparticles to reduce their immunogenicity and improve their pharmacokinetic and therapeutic properties. Here, we describe hybrid antibodies that can selectively deliver PEGylated medicines, imaging agents, or nanomedicines to target cells. Human IgG1 hybrid antibodies αPEG:αHER2 and αPEG:αCD19 were shown by ELISA, FACS, and plasmon resonance to bind to both PEG and HER2 receptors on SK-BR-3 breast adenocarcinoma and BT-474 breast ductal carcinoma cells or CD19 receptors on Ramos and Raji Burkitt's lymphoma cells. In addition, αPEG:αHER2 specifically targeted PEGylated proteins, liposomes, and nanoparticles to SK-BR-3 cells that overexpressed HER2, but not to HER2-negative MCF-7 breast adenocarcinoma cells. Endocytosis of PEGylated nanoparticles into SK-BR-3 cells was induced specifically by the αPEG:αHER2 hybrid antibody, as observed by confocal imaging of the accumulation of Qdots inside SK-BR-3 cells. Treatment of HER2(+) SK-BR-3 and BT-474 cancer cells with αPEG:αHER2 and the clinically used chemotherapeutic agent PEGylated liposomal doxorubicin for 3 hours enhanced the in vitro effectiveness of PEGylated liposomal doxorubicin by over two orders of magnitude. Hybrid anti-PEG antibodies offer a versatile and simple method to deliver PEGylated compounds to cellular locations and can potentially enhance the therapeutic efficacy of PEGylated medicines.
AuthorsHsin-Yi Tung, Yu-Cheng Su, Bing-Mae Chen, Pierre-Alain Burnouf, Wei-Chiao Huang, Kuo-Hsiang Chuang, Yu-Ting Yan, Tian-Lu Cheng, Steve R Roffler
JournalMolecular cancer therapeutics (Mol Cancer Ther) Vol. 14 Issue 6 Pg. 1317-26 (Jun 2015) ISSN: 1538-8514 [Electronic] United States
PMID25852063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright©2015 American Association for Cancer Research.
Chemical References
  • Antibodies
  • Antigens, CD19
  • Liposomes
  • Proteins
  • Polyethylene Glycols
  • Doxorubicin
  • Receptor, ErbB-2
Topics
  • Antibodies (metabolism)
  • Antigens, CD19 (metabolism)
  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Survival
  • Doxorubicin (metabolism)
  • Endocytosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Liposomes (metabolism)
  • MCF-7 Cells
  • Microscopy, Confocal
  • Nanomedicine (methods)
  • Nanoparticles
  • Neoplasms (metabolism, pathology)
  • Polyethylene Glycols (metabolism)
  • Protein Binding
  • Proteins (metabolism)
  • Receptor, ErbB-2 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: