biostudies-literatureMa YNCI NIH HHS962-70https://www.ebi.ac.uk/biostudies/studies/S-EPMC3831028biostudies-literatureUnknown6(9)The clinical application of siRNA is limited largely by the lack of efficient, cell-specific delivery systems. Antibodies are attractive delivery vehicles for targeted therapy due to their high specificity. In this study we describe the use of a humanized monoclonal antibody (mAb), hu3S193, against Lewis-Y (Le(y)), as a delivery vehicle for STAT3 siRNA. This mAb is rapidly internalized into Le(y)-expressing cancer cells via antigen recognition, and when coupled to STAT3 siRNA, a potentially powerful molecularly targeted delivery agent is created. Selective silencing of STAT3 is associated with tumor suppression. Two hu3S193 based siRNA delivery systems using STAT3 siRNA as a prototype were developed and tested in Le(y)-positive cancer cells: (a) a covalent construct based on a reductive diACS chemical biologyHumanized Lewis-Y specific antibody based delivery of STAT3 siRNA.PMC3831028P30 CA033572R01 CA055652Pillay VScott AMHorne DASimpson AJSwiderski PMMa YKowolik CMCaballero OLYu HKortylewski MJove RLee FTfalseHumanized Lewis-Y specific antibody based delivery of STAT3 siRNA.The clinical application of siRNA is limited largely by the lack of efficient, cell-specific delivery systems. Antibodies are attractive delivery vehicles for targeted therapy due to their high specificity. In this study we describe the use of a humanized monoclonal antibody (mAb), hu3S193, against Lewis-Y (Le(y)), as a delivery vehicle for STAT3 siRNA. This mAb is rapidly internalized into Le(y)-expressing cancer cells via antigen recognition, and when coupled to STAT3 siRNA, a potentially powerful molecularly targeted delivery agent is created. Selective silencing of STAT3 is associated with tumor suppression. Two hu3S193 based siRNA delivery systems using STAT3 siRNA as a prototype were developed and tested in Le(y)-positive cancer cells: (a) a covalent construct based on a reductive di2011-01-01T00:00:00Z2011 Sep2025-04-04T19:32:08.366Z2019-03-27T03:08:42ZS-EPMC38310282176684010.1021/cb200176v