Genetic delivery of the murine equivalent of bevacizumab (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, to suppress growth of human tumors in immunodeficient mice

Masaki Watanabe, Julie L. Boyer, Neil R. Hackett, Jianping Qiu, Ronald Crystal

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) produced by tumor cells plays a central role in stimulating angiogenesis required for solid tumor growth. VEGF-specific antibodies inhibit tumor cell line growth in animal models and a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]) is approved as a treatment for metastatic cancer. We hypothesized that administration of an adenoviral (Ad) vector expressing the murine monoclonal antibody equivalent of bevacizumab would suppress human tumor growth in vivo. The Ad vector (AdαVEGF) encodes the light chain and heavy chain cDNAs of monoclonal antibody A.4.6.1, a murine antibody that specifically recognizes human VEGF with the same antigen-binding site as bevacizumab. AdαVEGF efficacy in vivo was evaluated with A-673 rhabdomyosarcoma and DU 145 prostate carcinoma cells in human tumor cell xenografts in SCID mice. For both tumor models, AdαVEGF directed the expression of high anti-human VEGF IgG antibody titers in vivo, the numbers of mitotic nuclei and blood vessels in the tumor were significantly decreased (p < 0.05), tumor growth was suppressed (p < 0.05), and there was increased survival (p < 0.005). Thus, AdαVEGF, encoding a murine monoclonal antibody that is the equivalent of bevacizumab, effectively suppresses the growth of human tumors, suggesting gene therapy as an alternative to bevacizumab monoclonal antibody therapy.

Original languageEnglish
Pages (from-to)300-310
Number of pages11
JournalHuman Gene Therapy
Volume19
Issue number3
DOIs
Publication statusPublished - 1 Mar 2008
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Monoclonal Antibodies
Growth
Neoplasms
Antibodies
Vascular Tissue Neoplasms
SCID Mice
Rhabdomyosarcoma
Bevacizumab
Tumor Cell Line
Heterografts
Genetic Therapy
Prostate
Animal Models
Complementary DNA
Immunoglobulin G
Binding Sites
Carcinoma
Light
Antigens

ASJC Scopus subject areas

  • Genetics

Cite this

Genetic delivery of the murine equivalent of bevacizumab (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, to suppress growth of human tumors in immunodeficient mice. / Watanabe, Masaki; Boyer, Julie L.; Hackett, Neil R.; Qiu, Jianping; Crystal, Ronald.

In: Human Gene Therapy, Vol. 19, No. 3, 01.03.2008, p. 300-310.

Research output: Contribution to journalArticle

@article{d58ef7e0e4ce499a88b8293c809327b8,
title = "Genetic delivery of the murine equivalent of bevacizumab (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, to suppress growth of human tumors in immunodeficient mice",
abstract = "Vascular endothelial growth factor (VEGF) produced by tumor cells plays a central role in stimulating angiogenesis required for solid tumor growth. VEGF-specific antibodies inhibit tumor cell line growth in animal models and a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]) is approved as a treatment for metastatic cancer. We hypothesized that administration of an adenoviral (Ad) vector expressing the murine monoclonal antibody equivalent of bevacizumab would suppress human tumor growth in vivo. The Ad vector (AdαVEGF) encodes the light chain and heavy chain cDNAs of monoclonal antibody A.4.6.1, a murine antibody that specifically recognizes human VEGF with the same antigen-binding site as bevacizumab. AdαVEGF efficacy in vivo was evaluated with A-673 rhabdomyosarcoma and DU 145 prostate carcinoma cells in human tumor cell xenografts in SCID mice. For both tumor models, AdαVEGF directed the expression of high anti-human VEGF IgG antibody titers in vivo, the numbers of mitotic nuclei and blood vessels in the tumor were significantly decreased (p < 0.05), tumor growth was suppressed (p < 0.05), and there was increased survival (p < 0.005). Thus, AdαVEGF, encoding a murine monoclonal antibody that is the equivalent of bevacizumab, effectively suppresses the growth of human tumors, suggesting gene therapy as an alternative to bevacizumab monoclonal antibody therapy.",
author = "Masaki Watanabe and Boyer, {Julie L.} and Hackett, {Neil R.} and Jianping Qiu and Ronald Crystal",
year = "2008",
month = "3",
day = "1",
doi = "10.1089/hum.2007.109",
language = "English",
volume = "19",
pages = "300--310",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "3",

}

TY - JOUR

T1 - Genetic delivery of the murine equivalent of bevacizumab (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, to suppress growth of human tumors in immunodeficient mice

AU - Watanabe, Masaki

AU - Boyer, Julie L.

AU - Hackett, Neil R.

AU - Qiu, Jianping

AU - Crystal, Ronald

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Vascular endothelial growth factor (VEGF) produced by tumor cells plays a central role in stimulating angiogenesis required for solid tumor growth. VEGF-specific antibodies inhibit tumor cell line growth in animal models and a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]) is approved as a treatment for metastatic cancer. We hypothesized that administration of an adenoviral (Ad) vector expressing the murine monoclonal antibody equivalent of bevacizumab would suppress human tumor growth in vivo. The Ad vector (AdαVEGF) encodes the light chain and heavy chain cDNAs of monoclonal antibody A.4.6.1, a murine antibody that specifically recognizes human VEGF with the same antigen-binding site as bevacizumab. AdαVEGF efficacy in vivo was evaluated with A-673 rhabdomyosarcoma and DU 145 prostate carcinoma cells in human tumor cell xenografts in SCID mice. For both tumor models, AdαVEGF directed the expression of high anti-human VEGF IgG antibody titers in vivo, the numbers of mitotic nuclei and blood vessels in the tumor were significantly decreased (p < 0.05), tumor growth was suppressed (p < 0.05), and there was increased survival (p < 0.005). Thus, AdαVEGF, encoding a murine monoclonal antibody that is the equivalent of bevacizumab, effectively suppresses the growth of human tumors, suggesting gene therapy as an alternative to bevacizumab monoclonal antibody therapy.

AB - Vascular endothelial growth factor (VEGF) produced by tumor cells plays a central role in stimulating angiogenesis required for solid tumor growth. VEGF-specific antibodies inhibit tumor cell line growth in animal models and a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]) is approved as a treatment for metastatic cancer. We hypothesized that administration of an adenoviral (Ad) vector expressing the murine monoclonal antibody equivalent of bevacizumab would suppress human tumor growth in vivo. The Ad vector (AdαVEGF) encodes the light chain and heavy chain cDNAs of monoclonal antibody A.4.6.1, a murine antibody that specifically recognizes human VEGF with the same antigen-binding site as bevacizumab. AdαVEGF efficacy in vivo was evaluated with A-673 rhabdomyosarcoma and DU 145 prostate carcinoma cells in human tumor cell xenografts in SCID mice. For both tumor models, AdαVEGF directed the expression of high anti-human VEGF IgG antibody titers in vivo, the numbers of mitotic nuclei and blood vessels in the tumor were significantly decreased (p < 0.05), tumor growth was suppressed (p < 0.05), and there was increased survival (p < 0.005). Thus, AdαVEGF, encoding a murine monoclonal antibody that is the equivalent of bevacizumab, effectively suppresses the growth of human tumors, suggesting gene therapy as an alternative to bevacizumab monoclonal antibody therapy.

UR - http://www.scopus.com/inward/record.url?scp=41149156002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41149156002&partnerID=8YFLogxK

U2 - 10.1089/hum.2007.109

DO - 10.1089/hum.2007.109

M3 - Article

VL - 19

SP - 300

EP - 310

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 3

ER -