Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme

Veeravagu, Anand; Liu, Zhaofei; Niu, Gang; Chen, Kai; Jia, Bing; Cai, Weibo; Jin, Cunjing; Hsu, Andrew R.; Connolly, Andrew J.; Tse, Victor; Wang, Fan; Chen, Xiaoyuan

doi:10.1158/1078-0432.ccr-08-0797

Cited by 74 publications

(57 citation statements)

References 49 publications

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“…Glioblastoma multiforme (GBM) is a highly invasive brain tumor that is unvaryingly fatal in humans, despite even aggressive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy [24][25][26]. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma-related deaths.…”

Section: Discussionmentioning

confidence: 99%

A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth

Yuan¹,

Shen²,

Su³

et al. 2015

J Neurooncol

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Malignant glioma is among the most challenging of all cancers to treat successfully. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. In this study, we constructed a novel nanoparticle containing neuritin peptide with grp170. The nanoparticle could elicit a neuritin-specific cytotoxic T lymphocyte response to lyse glioma cells in vitro. In addition, the nanoparticle could inhibit tumor growth and improve the lifespan of tumor-bearing mice in vivo. Taken together, the results demonstrated that the nanoparticle can inhibit tumor growth and represents a promising therapy for glioma.

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Section: Discussionmentioning

confidence: 99%

A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth

Yuan¹,

Shen²,

Su³

et al. 2015

J Neurooncol

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“…Vascular niche and CSCs represent integral parts of the cancer facilitating invasion and expansion. 73 Calabrese and collegues identified a population of Nestin þ / Cd133þ cells located in areas of increased microvessels density. 24 These cells were proliferating and distributed into the brain towards endothelial vascular tubes.…”

Section: Glioblastoma Subtypesmentioning

confidence: 97%

Glioblastoma cancer stem cells: heterogeneity, microenvironment and related therapeutic strategies

Denysenko

Gennero

Roos

et al. 2010

Cell Biochemistry & Function

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Glioblastoma Multiforme (GBM) is an incurable malignancy. GBM patients have a short life expectancy despite aggressive therapeutic approaches based on surgical resection followed by adjuvant radiotherapy and concomitant chemotherapy. Glioblastoma growth is characterized by a high motility of tumour cells, their resistance to both chemo/radio-therapy, apoptosis inhibition leading to failure of conventional therapy. Cancer Stem Cells (CSCs), identified in GBM as well as in many other cancer types, express the membrane antigen prominin-1 (namely CD133). These cells and normal Neural Stem Cells (NSC) share surface markers and properties, i.e. are able to self-renew and differentiate into multiple cell types. Stem cell self-renewal depends on microenvironmental cues, including Extracellular Matrix (ECM) composition and cell types. Therefore, the role of microenvironment needs to be evaluated to clarify its importance in tumour initiation and progression through CSCs. The specific microenvironment of CSCs was found to mimic in part the vascular niche of normal stem cells. The targeting of GMB CSCs may represent a powerful treatment approach. Lastly, in GBM patients cancer-initiating cells contribute to the profound immune suppression that in turn correlated with CSCs STAT3 (CD133 + ). Further studies of microenvironment are needed to better understand the origin of GMB/GBM CSCs and its immunosuppressive properties.

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“…The distribution of the antibody was found high in liver and spleen and serum t 1/2 of 90 Y-DOTA-Abegrin was found to be 12-24 hours. The maximum dose tolerated was 200 µCi with maximum antitumor efficacy and no toxicity was observed with good hepatic clearance [30]. The success of radio labelled imaging in vitro and in vivo studies of Abegrin using radionuclides provides the success in to clinic to evaluate the tumor targeting efficacy, dose optimization, dose interval and pharmacokinetics of MEDI-522.…”

Section: Integrin Antagonists In Tumor and Angiogenesis Inhibitionmentioning

confidence: 99%

Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Santhosh¹

2014

J Cell Sci Ther

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Integrins are heterodimeric molecules that are composed of 18 α-subunits and 8 β-subunits. They exist in 24 distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases can result in enhanced tumorigenesis. Among several types of integrins, αvβ3 and α 5 β 1 have gained importance in anti-angiogenesis studies.Hence the role of antiangiogenesis antagonists has come into light. These include a variety of monoclonal antibodies and peptides. Each one of them has their own mechanism of action and antiangiogenesis activity. Current review aims at studying the phase 1 and 2 trails of these antagonists for anti-angiogenic function.

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Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme

Abstract: Purpose: Abegrin is a monoclonal antibody to human integrin a V h 3 , a cell adhesion molecule highly expressed on actively angiogenic endothelium and glioblastoma multiforme tumor cells. The purpose of this study was to evaluate the efficacy of a novel

Cited by 74 publications

References 49 publications

A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth

A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth

Glioblastoma cancer stem cells: heterogeneity, microenvironment and related therapeutic strategies

Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

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