Establishment and Evaluation of Cancer-Specific Human Monoclonal Antibody GAH for Targeting Chemotherapy Using Immunoliposomes
| Autor: | Toshiaki Tagawa, Yoko Hirakawa, Kazuhiro Nagaike, Katsuhiko Nohga, Saiko Hosokawa, Hisae Niki, Norihiko Ito |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Colorectal cancer
medicine.drug_class Molecular Sequence Data Immunology Monoclonal antibody Mice Stomach Neoplasms Tumor Cells Cultured Genetics medicine Animals Humans Doxorubicin Amino Acid Sequence Stomach cancer Drug Carriers Hybridomas Microscopy Confocal biology Antibodies Monoclonal Cancer medicine.disease Immunohistochemistry Molecular biology Endocytosis Colonic Neoplasms Liposomes Cancer cell biology.protein Lymph Nodes Antibody medicine.drug |
| Zdroj: | Hybridoma and Hybridomics. 23:109-120 |
| ISSN: | 1536-8599 |
| DOI: | 10.1089/153685904774129711 |
| Popis: | To establish human monoclonal antibodies suitable for targeting chemotherapy, we prepared a panel of human-mouse hybridomas, using mouse myelomas and lymphocytes of regional lymph nodes excised from cancer patients, and selected antibodies on the basis of their specificity of binding to the surface of viable cancer cells derived from fresh cancer tissues. A selected antibody, named GAH, was found to react with viable cancer cells from 21/22 stomach and 13/20 colon cancer tissues. As for further analysis, complementary DNAs encoding GAH were cloned and recombinant GAH (rGAH) was obtained from established CHO cells transfected with GAH expression vectors. rGAH selectively stained cancer cells in human tissue sections from 13/14 stomach, 4/11 colon, 5/11 mammary, and 0/7 lung cancers, while no positive staining was observed in those of non-tumor and various normal specimens. Notably, using confocal fluorescence microscopy, rGAH was not only bound to the surface of cancer cells, but was also internalized by the cells. The potential of rGAH for intracellular drug delivery was subsequently evaluated using rGAH-conjugated, doxorubicin (DXR)-encapsulated immunoliposomes. The immunoliposomes were also internalized into the cancer cells and finally DXR was delivered to the cell nucleus. Furthermore, the immunoliposomes could inhibit the growth of DXR-insensitive stomach cancer cells (B37) in an in vivo model. These results suggest that a GAH-utilized liposome-targeting technique will provide a potent and useful cancer chemotherapy with broad applications for cancer patients. |
| Databáze: | OpenAIRE |
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