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Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells
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Zeitschriftentitel: | Molecular Cancer Therapeutics |
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Personen und Körperschaften: | , , , , , , , |
In: | Molecular Cancer Therapeutics, 6, 2007, 10, S. 2737-2746 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Association for Cancer Research (AACR)
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Schlagwörter: |
author_facet |
Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin |
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author |
Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin |
spellingShingle |
Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin Molecular Cancer Therapeutics Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells Cancer Research Oncology |
author_sort |
roth, audrey |
spelling |
Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-07-0140 <jats:title>Abstract</jats:title> <jats:p>Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellulary delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line–dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. [Mol Cancer Ther 2007;6(10):2737–46]</jats:p> Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells Molecular Cancer Therapeutics |
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10.1158/1535-7163.mct-07-0140 |
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American Association for Cancer Research (AACR), 2007 |
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2007 |
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American Association for Cancer Research (AACR) |
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Molecular Cancer Therapeutics |
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title |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_unstemmed |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_full |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_fullStr |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_full_unstemmed |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_short |
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_sort |
anti-cd166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
topic |
Cancer Research Oncology |
url |
http://dx.doi.org/10.1158/1535-7163.mct-07-0140 |
publishDate |
2007 |
physical |
2737-2746 |
description |
<jats:title>Abstract</jats:title>
<jats:p>Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellulary delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line–dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. [Mol Cancer Ther 2007;6(10):2737–46]</jats:p> |
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author | Roth, Audrey, Drummond, Daryl C., Conrad, Fraser, Hayes, Mark E., Kirpotin, Dmitri B., Benz, Christopher C., Marks, James D., Liu, Bin |
author_facet | Roth, Audrey, Drummond, Daryl C., Conrad, Fraser, Hayes, Mark E., Kirpotin, Dmitri B., Benz, Christopher C., Marks, James D., Liu, Bin, Roth, Audrey, Drummond, Daryl C., Conrad, Fraser, Hayes, Mark E., Kirpotin, Dmitri B., Benz, Christopher C., Marks, James D., Liu, Bin |
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container_title | Molecular Cancer Therapeutics |
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description | <jats:title>Abstract</jats:title> <jats:p>Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellulary delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line–dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. [Mol Cancer Ther 2007;6(10):2737–46]</jats:p> |
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spelling | Roth, Audrey Drummond, Daryl C. Conrad, Fraser Hayes, Mark E. Kirpotin, Dmitri B. Benz, Christopher C. Marks, James D. Liu, Bin 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-07-0140 <jats:title>Abstract</jats:title> <jats:p>Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellulary delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line–dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. [Mol Cancer Ther 2007;6(10):2737–46]</jats:p> Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells Molecular Cancer Therapeutics |
spellingShingle | Roth, Audrey, Drummond, Daryl C., Conrad, Fraser, Hayes, Mark E., Kirpotin, Dmitri B., Benz, Christopher C., Marks, James D., Liu, Bin, Molecular Cancer Therapeutics, Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells, Cancer Research, Oncology |
title | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_full | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_fullStr | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_full_unstemmed | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_short | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_sort | anti-cd166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
title_unstemmed | Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells |
topic | Cancer Research, Oncology |
url | http://dx.doi.org/10.1158/1535-7163.mct-07-0140 |