author_facet Rein, Daniel T.
Breidenbach, Martina
Wu, Hongju
Han, Tie
Haviv, Yosef S.
Wang, Minghui
Kirby, Tyler O.
Kawakami, Yosuke
Dall, Peter
Alvarez, Ronald D.
Curiel, David T.
Rein, Daniel T.
Breidenbach, Martina
Wu, Hongju
Han, Tie
Haviv, Yosef S.
Wang, Minghui
Kirby, Tyler O.
Kawakami, Yosuke
Dall, Peter
Alvarez, Ronald D.
Curiel, David T.
author Rein, Daniel T.
Breidenbach, Martina
Wu, Hongju
Han, Tie
Haviv, Yosef S.
Wang, Minghui
Kirby, Tyler O.
Kawakami, Yosuke
Dall, Peter
Alvarez, Ronald D.
Curiel, David T.
spellingShingle Rein, Daniel T.
Breidenbach, Martina
Wu, Hongju
Han, Tie
Haviv, Yosef S.
Wang, Minghui
Kirby, Tyler O.
Kawakami, Yosuke
Dall, Peter
Alvarez, Ronald D.
Curiel, David T.
International Journal of Cancer
Gene transfer to cervical cancer with fiber‐modified adenoviruses
Cancer Research
Oncology
author_sort rein, daniel t.
spelling Rein, Daniel T. Breidenbach, Martina Wu, Hongju Han, Tie Haviv, Yosef S. Wang, Minghui Kirby, Tyler O. Kawakami, Yosuke Dall, Peter Alvarez, Ronald D. Curiel, David T. 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.20295 <jats:title>Abstract</jats:title><jats:p>Successful adenoviral (Ad) vector–mediated strategies for cancer gene therapy mandate gene‐delivery systems that are capable of achieving efficient gene delivery <jats:italic>in vivo.</jats:italic> In many cancer types, <jats:italic>in vivo</jats:italic> gene‐transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR‐independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene‐transfer efficiency of fiber‐modified Ads. Of the fiber‐modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene‐transfer efficiency <jats:italic>in vitro.</jats:italic> Gene‐delivery efficiency <jats:italic>in vivo</jats:italic> was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting <jats:italic>in vivo,</jats:italic> resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double‐modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer substrates, while the infectivity of nontarget cells in the mouse is not increased and comparable to Ad5. The fiber‐modified virus described here can help achieve higher clinical efficacy of cervical cancer gene therapy. © 2004 Wiley‐Liss, Inc.</jats:p> Gene transfer to cervical cancer with fiber‐modified adenoviruses International Journal of Cancer
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series International Journal of Cancer
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title Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_unstemmed Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_full Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_fullStr Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_full_unstemmed Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_short Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_sort gene transfer to cervical cancer with fiber‐modified adenoviruses
topic Cancer Research
Oncology
url http://dx.doi.org/10.1002/ijc.20295
publishDate 2004
physical 698-704
description <jats:title>Abstract</jats:title><jats:p>Successful adenoviral (Ad) vector–mediated strategies for cancer gene therapy mandate gene‐delivery systems that are capable of achieving efficient gene delivery <jats:italic>in vivo.</jats:italic> In many cancer types, <jats:italic>in vivo</jats:italic> gene‐transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR‐independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene‐transfer efficiency of fiber‐modified Ads. Of the fiber‐modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene‐transfer efficiency <jats:italic>in vitro.</jats:italic> Gene‐delivery efficiency <jats:italic>in vivo</jats:italic> was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting <jats:italic>in vivo,</jats:italic> resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double‐modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer substrates, while the infectivity of nontarget cells in the mouse is not increased and comparable to Ad5. The fiber‐modified virus described here can help achieve higher clinical efficacy of cervical cancer gene therapy. © 2004 Wiley‐Liss, Inc.</jats:p>
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author Rein, Daniel T., Breidenbach, Martina, Wu, Hongju, Han, Tie, Haviv, Yosef S., Wang, Minghui, Kirby, Tyler O., Kawakami, Yosuke, Dall, Peter, Alvarez, Ronald D., Curiel, David T.
author_facet Rein, Daniel T., Breidenbach, Martina, Wu, Hongju, Han, Tie, Haviv, Yosef S., Wang, Minghui, Kirby, Tyler O., Kawakami, Yosuke, Dall, Peter, Alvarez, Ronald D., Curiel, David T., Rein, Daniel T., Breidenbach, Martina, Wu, Hongju, Han, Tie, Haviv, Yosef S., Wang, Minghui, Kirby, Tyler O., Kawakami, Yosuke, Dall, Peter, Alvarez, Ronald D., Curiel, David T.
author_sort rein, daniel t.
container_issue 5
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container_title International Journal of Cancer
container_volume 111
description <jats:title>Abstract</jats:title><jats:p>Successful adenoviral (Ad) vector–mediated strategies for cancer gene therapy mandate gene‐delivery systems that are capable of achieving efficient gene delivery <jats:italic>in vivo.</jats:italic> In many cancer types, <jats:italic>in vivo</jats:italic> gene‐transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR‐independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene‐transfer efficiency of fiber‐modified Ads. Of the fiber‐modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene‐transfer efficiency <jats:italic>in vitro.</jats:italic> Gene‐delivery efficiency <jats:italic>in vivo</jats:italic> was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting <jats:italic>in vivo,</jats:italic> resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double‐modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer substrates, while the infectivity of nontarget cells in the mouse is not increased and comparable to Ad5. The fiber‐modified virus described here can help achieve higher clinical efficacy of cervical cancer gene therapy. © 2004 Wiley‐Liss, Inc.</jats:p>
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spelling Rein, Daniel T. Breidenbach, Martina Wu, Hongju Han, Tie Haviv, Yosef S. Wang, Minghui Kirby, Tyler O. Kawakami, Yosuke Dall, Peter Alvarez, Ronald D. Curiel, David T. 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.20295 <jats:title>Abstract</jats:title><jats:p>Successful adenoviral (Ad) vector–mediated strategies for cancer gene therapy mandate gene‐delivery systems that are capable of achieving efficient gene delivery <jats:italic>in vivo.</jats:italic> In many cancer types, <jats:italic>in vivo</jats:italic> gene‐transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR‐independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene‐transfer efficiency of fiber‐modified Ads. Of the fiber‐modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene‐transfer efficiency <jats:italic>in vitro.</jats:italic> Gene‐delivery efficiency <jats:italic>in vivo</jats:italic> was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting <jats:italic>in vivo,</jats:italic> resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double‐modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer substrates, while the infectivity of nontarget cells in the mouse is not increased and comparable to Ad5. The fiber‐modified virus described here can help achieve higher clinical efficacy of cervical cancer gene therapy. © 2004 Wiley‐Liss, Inc.</jats:p> Gene transfer to cervical cancer with fiber‐modified adenoviruses International Journal of Cancer
spellingShingle Rein, Daniel T., Breidenbach, Martina, Wu, Hongju, Han, Tie, Haviv, Yosef S., Wang, Minghui, Kirby, Tyler O., Kawakami, Yosuke, Dall, Peter, Alvarez, Ronald D., Curiel, David T., International Journal of Cancer, Gene transfer to cervical cancer with fiber‐modified adenoviruses, Cancer Research, Oncology
title Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_full Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_fullStr Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_full_unstemmed Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_short Gene transfer to cervical cancer with fiber‐modified adenoviruses
title_sort gene transfer to cervical cancer with fiber‐modified adenoviruses
title_unstemmed Gene transfer to cervical cancer with fiber‐modified adenoviruses
topic Cancer Research, Oncology
url http://dx.doi.org/10.1002/ijc.20295