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Targeted gene therapy of LS174 T human colon carcinoma by anti-TAG-72 immunoliposomes.
- Source :
-
Cancer Gene Therapy . May2008, Vol. 15 Issue 5, p331-340. 10p. 4 Black and White Photographs, 1 Chart, 3 Graphs. - Publication Year :
- 2008
-
Abstract
- Anti-tumor-associated glycoprotein (TAG)-72 PEG-immunoliposomes (PILs) were prepared by conjugation of Fab′ fragments of recombinant humanized monoclonal antibody, HuCC49, to sterically stabilize unilamellar liposomes (90–110 nm in diameter) to target TAG-72-overexpressing cancer cells. The liposomes consisted of 1-palmitonyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), 92 mol percent, O,O′-dymyrisyl-N-lysyl aspartate (DMKD cationic lipid), 4 mol percent, distearoyl-phosphatidyl-ethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), 3 mol percent and DSPE-maleimide (DSPE-PEG2000-Mal), 1 mol percent. These anti-TAG-72 PILs were able to adhere to the surface of TAG-72-overexpressing LS174 T human colon cancer cells more effectively than conventional liposomes. Also, in vitro gene transfection of the LS174 T cells by the anti-TAG-72 PILs in the presence of a high concentration of fetal bovine serum (up to 60%) was greater than that by conventional cationic lipoplexes. Intravenously administered anti-TAG-72 PILs efficiently localized in the LS174 T tumor tissues, while the non-targeted conventional liposomes did not. Intravenous administration of the anti-TAG-72 PILs containing plasmids encoding antiangiogenic proteins, such as angiostatin K1/3, endostatin and saxatilin, significantly inhibited in vivo growth of LS174 T tumors and angiogenesis in the tumor tissues. These results demonstrated the potential of TAG-72-mediated targeting of immunoliposomes as a modality for systemic gene delivery to human colon cancer cells.Cancer Gene Therapy (2008) 15, 331–340; doi:10.1038/cgt.2008.11; published online 29 February 2008 [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNOGLOBULINS
*COLON cancer
*GENE therapy
*GENETIC engineering
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 09291903
- Volume :
- 15
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cancer Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 31579046
- Full Text :
- https://doi.org/10.1038/cgt.2008.11