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Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , |
| In: | Cancer Research, 64, 2004, 18, S. 6616-6625 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. |
|---|---|
| author |
Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. |
| spellingShingle |
Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. Cancer Research Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies Cancer Research Oncology |
| author_sort |
bocci, guido |
| spelling |
Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-04-0401 <jats:title>Abstract</jats:title> <jats:p>A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non–tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.</jats:p> Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies Cancer Research |
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American Association for Cancer Research (AACR), 2004 |
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American Association for Cancer Research (AACR), 2004 |
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0008-5472 1538-7445 |
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0008-5472 1538-7445 |
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| title |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_unstemmed |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_full |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_fullStr |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_full_unstemmed |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_short |
Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_sort |
increased plasma vascular endothelial growth factor (vegf) as a surrogate marker for optimal therapeutic dosing of vegf receptor-2 monoclonal antibodies |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-04-0401 |
| publishDate |
2004 |
| physical |
6616-6625 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non–tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.</jats:p> |
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| author | Bocci, Guido, Man, Shan, Green, Shane K., Francia, Giulio, Ebos, John M. L., du Manoir, Jeanne M., Weinerman, Adina, Emmenegger, Urban, Ma, Li, Thorpe, Philip, Davidoff, Andrew, Huber, James, Hicklin, Daniel J., Kerbel, Robert S. |
| author_facet | Bocci, Guido, Man, Shan, Green, Shane K., Francia, Giulio, Ebos, John M. L., du Manoir, Jeanne M., Weinerman, Adina, Emmenegger, Urban, Ma, Li, Thorpe, Philip, Davidoff, Andrew, Huber, James, Hicklin, Daniel J., Kerbel, Robert S., Bocci, Guido, Man, Shan, Green, Shane K., Francia, Giulio, Ebos, John M. L., du Manoir, Jeanne M., Weinerman, Adina, Emmenegger, Urban, Ma, Li, Thorpe, Philip, Davidoff, Andrew, Huber, James, Hicklin, Daniel J., Kerbel, Robert S. |
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| description | <jats:title>Abstract</jats:title> <jats:p>A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non–tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.</jats:p> |
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| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| spelling | Bocci, Guido Man, Shan Green, Shane K. Francia, Giulio Ebos, John M. L. du Manoir, Jeanne M. Weinerman, Adina Emmenegger, Urban Ma, Li Thorpe, Philip Davidoff, Andrew Huber, James Hicklin, Daniel J. Kerbel, Robert S. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-04-0401 <jats:title>Abstract</jats:title> <jats:p>A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non–tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.</jats:p> Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies Cancer Research |
| spellingShingle | Bocci, Guido, Man, Shan, Green, Shane K., Francia, Giulio, Ebos, John M. L., du Manoir, Jeanne M., Weinerman, Adina, Emmenegger, Urban, Ma, Li, Thorpe, Philip, Davidoff, Andrew, Huber, James, Hicklin, Daniel J., Kerbel, Robert S., Cancer Research, Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies, Cancer Research, Oncology |
| title | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_full | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_fullStr | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_full_unstemmed | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_short | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| title_sort | increased plasma vascular endothelial growth factor (vegf) as a surrogate marker for optimal therapeutic dosing of vegf receptor-2 monoclonal antibodies |
| title_unstemmed | Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-04-0401 |