Bevacizumab Overview

Introduction of Bevacizumab

Bevacizumab is a recombinant humanized monoclonal antibody (mAb) that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). Bevacizumab was originally derived from a mouse mAb generated from mice immunized with the 165-residue- form of recombinant human vascular endothelial growth factor (VEGF). It was humanized by retaining the binding region and replacing the rest with a human full light chain and a human truncated IgG1 heavy chain, with some other substitutions. The resulting plasmid was transfected into Chinese Hamster Ovary (CHO) cells which are grown in industrial fermentation systems. As the first available angiogenesis inhibitor in the United States, bevacizumab was approved for medical use by the Food and Drug Administration (FDA) in 2004. Bevacizumab has been successively approved for the treatment of colorectal cancer, Lung cancer, breast cancer, renal cancers, brain cancers, and ovarian cancer. Bevacizumab was also found to be effective against eye diseases such as age-related macular degeneration. Bevacizumab is now marketed by Hoffmann-La Roche and Amgen Inc. respectively with the trade name Avastin and Mvasi.

Mechanism of Action of Bevacizumab

Angiogenesis is a very complex and highly regulated process by which tumors larger than 1 mm are thought to develop new vasculature. This constitutes an essential feature of cancer, considering that in order for cancer cells to proliferate, a continuous supply of oxygen is needed. Without neovascularization, tumor growth is arrested. The mechanisms through which tumors acquire neovascularity are (a) endothelial ‘‘sprouting,’’ wherein normal luminal endothelial cells migrate through the basement membrane into the underlying extracellular matrix and to the tumor, developing a morphology that resembles plant sprouts; (b) co-option of pre-existing vasculature, wherein tumor cells grow around blood vessels; (c) vasculogenic mimicry, wherein aggressive tumor cells develop microvascular channels; and (d) tumor neovascularization per se, wherein the release of proangiogenic factors, such as VEGF, fibroblast growth factor, and platelet-derived growth factor (PDGF), by endothelial, stromal, and tumor cells, causes endothelial activation, vessel growth, and tumor expansion. The VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor 1 and 2) and their corresponding VEGF tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) have emerged as promising targets because they have an important role in angiogenesis and in the growth of tumors. This is especially true of serum VEGF-A, the levels of which are higher in tumor tissue than in normal tissue, specifically in cancers of the breast, lung, colon, uterus, and ovary, which has been associated with poor prognosis. When VEGF-A binds to its receptor (VEGFR-2 and less specifically to VEGFR1), it activates a signaling cascade mediated by MAP kinase and PI3K/Akt/mTOR that results in the development of angiogenesis, increased vascular permeability, and lymphangiogenesis. Bevacizumab binds to VEGF-A, and thereby inhibits the binding of VEGF-A to its receptors on the surface of endothelial cells. Neutralizing the biological activity of VEGF regresses the vascularization of tumors, normalizes remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth.

Fig.1 Mechanism of action of Bevacizumab

Table 1. Clinical Projects of Bevacizumab*

Table 2. Approved Drugs of Bevacizumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Avastin	Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms, Renal Cell Ovarian Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Genentech	February 26, 2004
Avastin	Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms, Renal Cell Ovarian Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Roche Registration GmbH	January 12, 2005
Avastin	Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms, Renal Cell Ovarian Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Hoffmann-La Roche Limited	November 2, 2005
Avastin	Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms, Renal Cell Ovarian Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Roche Products Pty Ltd	May 17, 2018
Avastin	Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms, Renal Cell Ovarian Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Chugai Pharmaceutical Co., Ltd	April 18, 2007
Mvasi	Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Ovarian Neoplasms, Peritoneal Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Amgen Inc	September 14, 2017
Mvasi	Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Ovarian Neoplasms, Peritoneal Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Amgen Europe B.V.	January 15, 2018
Mvasi	Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Ovarian Neoplasms, Peritoneal Neoplasms, Breast Neoplasms	Concentrate for solution	25 mg / mL	Intravenous infusion	Amgen Canada Inc	April 30, 2018

What We Provide

Therapeutic Antibody

Bevacizumab

We provide high-quality Bevacizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term= Bevacizumab

** Information presented in the table were collected from the following websites:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125085
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000582/human_med_000663.jsp
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004728/human_med_002217.jsp
http://search.tga.gov.au/s/search.html?collection=tga-artg&profile=record&meta_i=99757
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=75642
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=95974
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/4291413A1

For research use only. Not intended for any clinical use.