In vitro targeted killing of human endothelial cells by co-incubation of human serum and NGR peptide conjugated human albumin protein bearing alpha (1-3) galactose epitopes.
The NGR/alpha1,3Gal-HSA peptide was designed to specifically target CD13 positive cells and induce cell lysis. NGR is the targeting component of the peptide in that it binds the CD13 isoform (aminopeptidase) that is expressed in tumor vessels. Galactose alpha1,3-galactose terminal carbohydrate epitope (alpha1,3Gal) induces a strong antibody reaction in human and Old World Monkeys and in vivo, this reaction leads to organ rejection. The human serum albumin (HSA) bearing alpha1,3Gal epitope was therefore used to lyse cells. In the present study, we were able to demonstrate that NGR/alpha1,3Gal-HSA binds CD13 positive human umbilical vein endothelial cells (HUVEC). We also found by live/dead fluorescent staining that NGR/alpha1,3Gal-HSA was able to induce lysis of HUVECs upon incubation with human serum. Therefore, by conjugating NGR to HSA bearing alpha1,3Gal epitopes, we are able to specifically target and lyse cells expressing CD13. This strategy may be potentially useful in tumor anti-angiogenesis therapy.
Holle
Lori
L
Oncology Research Institute, Greenville Hospital System, Greenville, SC 29605, USA.
Song
Wendy
W
Hicks
Labri
L
Holle
Eric
E
Holmes
Lillian
L
Wei
Yanzhang
Y
Li
Jinhua
J
Wagner
Thomas
T
Yu
Xianzhong
X
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D018826:CD13 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms; D012709:Serum Albumin / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D000939:Epitopes; D010455:Peptides; D020033:Protein Isoforms; D012709:Serum Albumin; D018826:CD13 Antigens; D005690:Galactose