The Development Of Avastin
Published 2008 · Medicine
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Bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, USA) is a humanized monoclonal antibody that specifically targets and neutralizes vascular endothelial growth factor (VEGF-A), an essential endothelial cell mitogen and survival factor. As the first anti-angiogenic therapy developed and approved for human cancer, it represents the culmination of many years of biologic and human research in many laboratories and clinics around the world. This chapter will review (1) the development of bevacizumab beginning with the cloning of human VEGF which allowed for the generation of murine-derived, human-specific anti-VEGF monoclonal antibodies; (2) the process by which a single clone, A4.6.1, was identified and selected for clinical development; (3) the process of “humanizing” the murine antibody to form bevacizumab to enable human testing; (4) the clinical development program from phase I through phase III clini cal experiments; (5) the future areas for clinical evaluation of bevacizumab.respect to differential efficacy and adverse effect profiles.
This paper references
The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies.
K. Kim (1992)
Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer.
D. Johnson (2004)
A randomized phase III trial of paclitaxel with or without bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: Eastern cooperative oncology group trial E2100
R. Zon (2006)
Choriocarcinoma. Transfilter stimulation of vasoproliferation in the hamster cheek pouch. Studied by light and electron microscopy.
R. L. Ehrmann (1968)
Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.
B. Giantonio (2007)
Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.
L. Presta (1997)
COMPARISON OF FOUR CHEMOTHERAPY REGIMENS FOR ADVANCED NON–SMALL-CELL LUNG CANCER
Replacing the complementarity-determining regions in a human antibody with those from a mouse
Peter T. Jones (1986)
Tumor angiogenesis: therapeutic implications.
J. Folkman (1971)
Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
A. Sandler (2006)
Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.
F. Kabbinavar (2003)
Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial.
M. Rothenberg (2003)
Vasculae Reactions of Normal and Malignant Tissues in Vivo. I. Vascular Reactions of Mice to Wounds and to Normal and Neoplastic Transplants
G. H. Algire (1945)
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
H. Hurwitz (2004)
Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique.
M. Greenblatt (1968)
Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
Y. Takahashi (1995)
The anti-angiogenic basis of metronomic chemotherapy
R. Kerbel (2004)
A hapten-specific chimaeric IgE antibody with human physiological effector function
M. Neuberger (1985)
Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.
A. de Gramont (2000)
Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
P. Piedbois (1998)
Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer.
K. Miller (2005)
Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group.
L. Saltz (2000)
Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer.
Y. Takahashi (1997)
Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks.
M. Green (2005)
Reshaping human antibodies for therapy
L. Riechmann (1988)
Molecular determinants in the biology of liver metastasis.
R. Radinsky (1996)
The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.
N. Petrelli (1989)
Humanization of an anti-p185HER2 antibody for human cancer therapy.
P. Carter (1992)
Transplacental carcinogenesis by stilbestrol.
J. Folkman (1971)
A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.
J. Yang (2003)
Clinical benefit from bevacizumab (BV) in responding (R) and non-responding (NR) patients (pts) with metastatic colorectal cancer (mCRC)
R. Mass (2005)
Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma
R. Miller (1983)
Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo
K. J. Kim (1993)
Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis.
R. Warren (1995)
Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.
F. Kabbinavar (2005)
Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.
J. Blum (1999)
Vascular endothelial growth factor is a secreted angiogenic mitogen.
D. W. Leung (1989)
ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESIS
J. Folkman (1971)
Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer.
T. Tokunaga (1998)
The biology of vascular endothelial growth factor.
N. Ferrara (1997)
Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.
N. Ferrara (1993)
This paper is referenced by
In vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer.
Jin Cheon Kim (2009)