A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas

Li, Jia; Zhang, Zhiming; Lv, Lian‐Jie; Qiao, Haibo; Chen, Xiuju; Zou, Chao

doi:10.1016/j.bbrc.2016.02.035

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…In summary, the dismal prognosis of patients with glioblastoma motivates the development of new treatments. The Tspo is not only a mitochondrial in vivo marker for molecular imaging but also a target for novel TSPO-binding drugs [44][45][46] , some of which have already been shown to act synergistically with other anticancer drugs, such as 5-FU 37 .…”

Section: Histological Tissue Analysismentioning

confidence: 99%

Selective, high-contrast detection of syngeneic glioblastoma in vivo

Bánati

Wilcox

et al. 2020

Sci Rep

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Glioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour’s ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo−/− mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host’s glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO−/−) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma.

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Section: Histological Tissue Analysismentioning

confidence: 99%

Selective, high-contrast detection of syngeneic glioblastoma in vivo

Bánati

Wilcox

et al. 2020

Sci Rep

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“…Delivery of the construct of a bispecific Ab with an LDLR-binding domain of apoB to facilitate its transfer across the BBB and promoting alpha secretase activity over beta-secretase activity thus favoring the neuroprotective APP cleavage by alpha-secretase using an adenoviral vector has shown beneficial effects in a mouse model of AD [170]. In addition, targeting simultaneously the angiogenic factor angiopoietin-2 (Ang-2) and translocator protein (TSPO), both of which are overexpressed in bevacizumab-treated glioblastomas, with a bispecific Ab in bevacizumab-treated rats resulted in prolonged survival [171]. Furthermore, another bispecific Ab targeting Ang-2 and vascular endothelial growth factor (VEGF) was also found to prolong survival in a mouse model with glioblastoma xenografts, suggesting that bispecific Abs targeting appropriate epitopes may be beneficial in neurooncology [172].…”

Section: Bispecific Monoclonal Antibodiesmentioning

confidence: 99%

Monoclonal Antibodies as Neurological Therapeutics

et al. 2021

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Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

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“…Another strategy under preclinical development to improve antibody's efficacy is the use of bispecific antibodies (bsAbs), which recognize two different epitopes. For example, bsAbs targeting Agn-2 and TSPO or Ang-2 and VEGF extended the survival of murine GBM models, while stimulating the immune anti-tumor response [230,231]. A special type of bsAbs are the BiTEs, bispecific antibodies that link a TSA with a co-stimulatory molecule on a T-cell, establishing immunological synapses [227], such as BiTEs targeting EGRFvIII and the T-cell activation ligand CD3 [232,233].…”

Section: Specifically Egfr and Egfrviii Expression Is Heterogeneous mentioning

confidence: 99%

Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development

Garcia-Fabiani

Ventosa

Comba

et al. 2020

Expert Opinion on Investigational Drugs

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Introduction: Gliomas are infiltrating brain tumors associated with high morbidity and mortality. Current standard of care includes radiation, chemotherapy and surgical resection. Today, survival rates for malignant glioma patients remain dismal and unchanged for decades. The glioma microenvironment is highly immunosuppressive and consequently this has motivated the development of immunotherapies for counteracting this condition, enabling the immune cells within the tumor microenvironment to react against this tumor. Areas covered: The authors discuss immunotherapeutic strategies for glioma in phase-I/II clinical trials and illuminate their mechanisms of action, limitations and key challenges. They also examine promising approaches under preclinical development. Expert opinion: In the last decade there has been an expansion in immune-mediated anti-cancer therapies. In the glioma field, sophisticated strategies have been successfully implemented in preclinical models. Unfortunately, clinical trials have not yet yielded consistent results for glioma patients. This could be attributed to our limited understanding of the complex immune cell infiltration and its interaction with the tumor cells, the selected time for treatment, the combination with other therapies and the route of administration of the agent. Applying these modalities to treat malignant glioma is challenging, but many new alternatives are emerging to bypass these hurdles.

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A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas

Cited by 10 publications

References 20 publications

Selective, high-contrast detection of syngeneic glioblastoma in vivo

Selective, high-contrast detection of syngeneic glioblastoma in vivo

Monoclonal Antibodies as Neurological Therapeutics

Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development

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