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Targeted gene therapy of LS174 T human colon carcinoma by anti-TAG-72 immunoliposomes

Cancer Gene Therapy volume 15, pages 331–340 (2008)Cite this article

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.

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Acknowledgements

We wish to acknowledge the financial support of the Korea Research Foundation in the program year of 2005.

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Authors and Affiliations

  1. Department of Biomedical Laboratory Science, Institute of Health Science, Yonsei University, Wonju, Republic of Korea

    K S Kim, Y K Lee, J S Kim, K H Koo & Y S Park

  2. Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

    H J Hong

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Correspondence to Y S Park.

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Kim, K., Lee, Y., Kim, J. et al. Targeted gene therapy of LS174 T human colon carcinoma by anti-TAG-72 immunoliposomes. Cancer Gene Ther 15, 331–340 (2008). https://doi.org/10.1038/cgt.2008.11

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