Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells.
Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG-ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG-ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG-ADV and Herceptin immobilized PEG-ADV (HER-PEG-ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER-PEG-ADV exhibited more enhanced level of GFP expression than PEG-ADV did for MDA-MB-435 and MDA-MB-468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER-PEG-ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity.
Jung
Yukyung
Y
Department of Chemical Engineering, Yonsei University, 134 Shinchon-Dong Seodaemun-Gu, Seoul 120-749, South Korea.
Park
Hyo-Jin
HJ
Kim
Pyung-Hwan
PH
Lee
Jaewon
J
Hyung
Woochan
W
Yang
Jaemoon
J
Ko
Hyunju
H
Sohn
Joo-Hyuk
JH
Kim
Joo-Hang
JH
Huh
Yong-Min
YM
Yun
Chae-Ok
CO
Haam
Seungjoo
S
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008027:Light; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012542:Scattering, Radiation; D014161:Transduction, Genetic; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D049452:Green Fluorescent Proteins; D015850:Interleukin-6; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab