title: 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.
authors: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: Hsin-Yi
authors: HY
authors: Tung
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Yu-Cheng
authors: YC
authors: Su
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Bing-Mae
authors: BM
authors: Chen
authors: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: Pierre-Alain
authors: PA
authors: Burnouf
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Wei-Chiao
authors: WC
authors: Huang
authors: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
authors: Kuo-Hsiang
authors: KH
authors: Chuang
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Yu-Ting
authors: YT
authors: Yan
authors: Faculty of Biomedical Science and Environmental Biology, MedicoGenomic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. sroff@ibms.sinica.edu.tw tlcheng@kmu.edu.tw.
authors: Tian-Lu
authors: TL
authors: Cheng
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. sroff@ibms.sinica.edu.tw tlcheng@kmu.edu.tw.
authors: Steve R
authors: SR
authors: Roffler
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D018941:Antigens, CD19 / Q000378:metabolism; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000378:metabolism; D004705:Endocytosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D004317:Doxorubicin; D008081:Liposomes; D011092:Polyethylene Glycols; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases