Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth

Xuan, Zixue; Li, Lin-Na; Zhang, Qi; Xu, Chi; Yang, Dawei; Yuan, Ye; An, Yinghong; Wang, Shanshan; Li, Xiaowen; Yuan, Si-Ming

doi:10.3892/ijo.2014.2690

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…VEGFR2 can be a target in AITL therapy and anti-VEGFR2 antibody or VEGFR2 inhibitors have already been used in clinical studies and practice. They had attenuated tumor angiogenesis and inhibited the tumor growth,33,34 and had a synergistic effect with chemotherapy 35,36. Recombinant human endostatin also can exert anti-angiogenic activity by directly interacting with VEGFR2 of endothelial cells 13.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma

Zhang

Cao

Xue

et al. 2016

OTT

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Peripheral T cell lymphoma (PTCL) has a poor prognosis. Overexpression of vascular endothelial growth factor (VEGF) might contribute to the poor prognosis of PTCL and could be the target of novel therapy. The efficacy and safety of recombinant human endostatin (Endostar) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (ECHOP) have been explored in 15 PTCL patients. The objective response rate was 80%, with 53.3% patients having achieved complete response (CR) rate. The CR rate was 100% (3/3) in angioimmunoblastic T cell lymphoma (AITL) patients compared to only 36.4% (4/11) in PTCL not otherwise specified (PTCL-NOS) patients. With a median follow-up of 69 months, the 5-year progression-free survival and overall survival (OS) were 53% and 60%, respectively. The 5-year OS was 100% in AITL but was only 45% in PTCL-NOS. Seven out of 11 patients showed overexpression of VEGFR2 in their tumor vessels and had a better efficacy than those with low expression of VEGFR2. Grade 3 or 4 neutropenia is the most common toxicity observed. ECHOP was safe and might display potential benefit in AITL patients.

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Section: Discussionmentioning

confidence: 99%

Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma

Zhang

Cao

Xue

et al. 2016

OTT

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“…41 It has also been reported that, anti-VEGFR2 antibody was able to promote apoptosis in vivo. 42 These could account for the reason why the BiAb faliled in promoting apoptosis in HT-29 cells in vitro, but stimulated apoptosis in HT-29 tumor xenograft (Figs. 5 and 7).…”

Section: Discussionmentioning

confidence: 99%

A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity

Chen

Xie

Acheampong

et al. 2015

Cancer Biology & Therapy

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ABSRTRACTBoth Epidermal Growth Factor Receptor (EGFR) and the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) play critical roles in tumorigenesis. We hypothesized co-targeting EGFR and VEGFR2 using a bispecific antibody might have significant therapeutic potential. Here,we designed and produced a human IgG-like bispecific antibody (Bi-Ab) based on the variable regions of cetuximab (an anti-EGFR antibody) and mAb-04 (an anti-VEGFR2 antibody developed in our lab) . The Bi-Ab was found to inhibit the proliferation, survival and invasion of cancer cells via ablating phosphorylation of receptor and downstream signaling. In vivo efficacy was demonstrated against established HT-29 and SKOV-3 xenografts grown in nude mice. Studies revealed our Bi-Ab was able to restrain xenografted tumor growth and prolong survival of mice through inhibiting cell proliferation,promoting apoptosis and antiangiogenesis. In contrast to cetuximab or mAb-04 alone, our Bi-Ab exhibits enhanced antitumor activity and has equal or slightly superior activity to their combination (Combi). It shows promise as a therapeutic agent, especially for use against tumors EGFR and/or VEGFR2 over-expressing malignancies.

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“…Finally, mice were euthanized with an intraperitoneal injection of pentobarbital sodium (200 mg/kg) at the end of the experiment, then tumors were harvested and weighed. The expression of Ki67, caspase-3, cleaved-caspase-3, and CD31 in xenograft tumors was also detected by immunohistochemistry (IHC) staining (6).…”

Section: Methodsmentioning

confidence: 99%

“…BC001 is a novel fully humanized monoclonal antibody of VEGFR2. Our previous study showed that BC001 inhibited the growth of gastric cancer in vitro and in vivo (6); however, an AVAGAST trial showed that bevacizumab combined with chemotherapy could not significantly improve overall survival of patients with advanced gastric cancer, indicating that it is important to identify an effective BC001-combined therapeutic regimen for the treatment of gastric cancer (7). Numerousstudies have demonstrated that certain anti-angiogenic drugs could induce autophagy (8-10).…”

Section: Introductionmentioning

confidence: 99%

Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer

et al. 2019

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Gastric cancer is an important cancer type worldwide, the anti-angiogenic agent BC001 can target the vascular endothelial growth factor receptor 2 (VEGFR2), and significantly suppresses the growth of gastric cancer BGC823 cells in vitro and in vivo . However, numerous results indicated that antiangiogenic drugs could induce autophagy, and the inhibition of autophagy enhanced the anticancer effects of antiangiogenic agents. In the present study, hydroxychloroquine (HCQ), an inhibitor of autophagy, enhanced the antiproliferative and proapoptotic effects of BC001 in vitro . Furthermore, HCQ enhanced the antitumor effects of BC001 on BGC823 xenograft tumors in vivo . Of note, BC001 neither induced nor inhibited autophagy. RNA-sequencing results revealed that HCQ regulated autophagy or lysosomal-associated genes, such as tumor protein p53-inducible nuclear protein 1, interleukin (IL)1B, tumor necrosis factor (TNF), Mediterranean fever, ubiquitin specific peptidase 36, IL6, neuraminidase (NEU)1, ATP-binding cassette subfamily A member 1, proprotein convertase subtilisin/kexin type 9, myelin basic protein and NEU3. Importantly, HCQ was determined to affect multiple pathways, including 'negative regulation of endothelial cell proliferation', 'blood vessel remodeling', 'cell surface receptor signaling pathways' and 'notch receptor processing' associated with 'signal transduction', 'cancers' and 'immune system', through regulating C-X-C motif chemokine ligand 8, TNF, IL6, intercellular adhesion molecule 1 and FOS genes. In summary, HCQ was proposed to enhance the anticancer effects of BC001 in gastric cancer via complex mechanisms.

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Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth

Cited by 10 publications

References 41 publications

Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma

Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma

A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity

Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer

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