Construction and development of a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma

Feng, Li; Liu, Yanhong; Li, Yanwen; Li, Yuehui; Xie, Pingli; Ju, Qiang; Chen, Lin; Li, Guancheng

doi:10.1007/s00253-012-4243-5

Cited by 9 publications

(10 citation statements)

References 22 publications

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“…While previous studies have used GPI-anchored antibodies for high-throughput screening purposes and HIV inhibition in vitro, we report the use of antibodies anchored to the surface of cells as a prophylactic approach for lung infections 35 , 36 . Importantly, expressing anchored neutralizing antibodies on the surface of lung cells provides several benefits over systemic delivery by: (1) preventing the neutralizing antibody from diffusing away from the tissues infected by viruses, (2) raising the local concentration of antibody in the target organ, and (3) are likely increasing the persistence of antibodies on the mucosal surface.…”

Section: Discussionmentioning

confidence: 99%

Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

et al. 2018

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The lung is a critical prophylaxis target for clinically important infectious agents, including human respiratory syncytial virus (RSV) and influenza. Here, we develop a modular, synthetic mRNA-based approach to express neutralizing antibodies directly in the lung via aerosol, to prevent RSV infections. First, we express palivizumab, which reduces RSV F copies by 90.8%. Second, we express engineered, membrane-anchored palivizumab, which prevents detectable infection in transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and 89.6%, respectively. Finally, we express an anchored or secreted high-affinity, anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH, but not RSV sVHH, significantly inhibits RSV 7 days post transfection, and we show that RSV aVHH is present in the lung for at least 28 days. Overall, our data suggests that expressing membrane-anchored broadly neutralizing antibodies in the lungs could potentially be a promising pulmonary prophylaxis approach.

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Section: Discussionmentioning

confidence: 99%

Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

et al. 2018

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“…Li et al published the construction of a mammalian cell-based display library and chose GOLPH2 as first target [44]. This approach would lead to direct panning of full-length antibodies.…”

Section: Therapeutic Targeting Of Golph2mentioning

confidence: 99%

A review of GOLPH2, an oncogenic protein and novel therapeutic options for GOLPH2 driven tumours

Yang¹,

Liewen²,

Markuly³

et al. 2020

J Transl Sci

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GOLPH2 (Golgi Phosphoprotein 2) is a protein with pro-oncogenic properties that has currently been identified as a prime target for tumour therapy. Its involvement in key oncogenic pathways like EGFR, mTOR/AKT, PI3K makes it a good candidate for therapeutic intervention. Several research groups have consistently reported that GOLPH2, when expressed at high levels leads to epithelial to mesenchymal transition (EMT), increased cell proliferation, migration and metastasis.Not amazingly, it appears that many tumours exploit GOLPH2 for their advantage. Stopping GOLPH2´s detrimental effects would mean impairing tumour progression on various levels of its development. Therefore, inhibition of GOLPH2, a protein contributing to important hallmarks of cancer deserves the attention of researchers and drug developing stakeholders. However, its mainly intracellular localisation and the lack of domains that could possibly be interfered with by small molecules, have led to the conclusion that GOLPH2 is an un-targetable molecule.Here, we summarize the current knowledge of this multifunctional protein and describe possibilities to pharmacologically intervene to ameliorate its overshooting function in malignant diseases. Novel approaches like viral interventions or specific antibodies could soon result in a substantial therapeutic improvement for cancers with underlying GOLPH2 pathologies.

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“…In conclusion, mAbs and s-ELISA against Golph2 may be useful tools for the sensitive and specific diagnosis of HCC. The preparation of humanized antibody has been published previously (23), whereas the optimization of humanized antibody requires further research. This study provides the basis for optimization of humanized antibody.…”

Section: A B Cmentioning

confidence: 99%

Monoclonal antibody preparation of Golgi phosphoprotein 2 and preliminary application in the early diagnosis of hepatocellular carcinoma

Ju¹,

Zhao²,

Liu³

et al. 2013

Molecular Medicine Reports

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Golgi phosphoprotein 2 (Golph2) is a type II Golgi‑specific membrane protein, which has been found to be overexpressed in hepatocellular carcinoma (HCC) patients. The sensitivity of diagnosis of HCC using Golph2 (76%) was markedly elevated compared with alpha‑fetoprotein (AFP) (70%), and Golph2 is expected to be a novel and effective serum biomarker for the diagnosis of HCC. The aim of this study was to prepare monoclonal antibodies against Golph2 and to establish double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which will be used in diagnostics, therapeutics and as a tool in understanding the role of Golph2 in the pathogenesis of liver diseases and cancer. In this study, fusion protein TRX-Golph2 was expressed and purified using an Escherichia coli system. BALB/c mice were immunized with TRX-Golph2 recombinant protein. The hybridoma technique was used for the production of anti-Golph2 monoclonal antibody. Hybridoma clones were screened using indirect ELISA and anti-Golph2 monoclonal antibody was produced in the ascites of BALB/c mice. The specificity of anti-Golph2 monoclonal antibody was detected by western blot analysis and immunocytochemistry. s-ELISA was established using horseradish peroxidase (HRP)‑labeled anti-Golph2 monoclonal antibody and used to detect the antigen in the serum of HCC patients. As a result, five stable hybridoma cell clones (5C6D5, 5B7F5, 7F5F3, 8A7B4, 8C9E8) producing anti-Golph2 monoclonal antibody were established. The highest titer of anti-Golph2 monoclonal antibody (5C6D5) was 1:51,200. Western blot analysis revealed that anti-Golph2 monoclonal antibody had a high specificity for Golph2 protein. Anti-Golph2 monoclonal antibody was HRP-labeled and the optimal working concentration was found to be 1:500. The levels of antigen in a proportion of HCC patients were shown to be significantly higher compared to those found in healthy controls.

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Construction and development of a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma

Cited by 9 publications

References 22 publications

Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

A review of GOLPH2, an oncogenic protein and novel therapeutic options for GOLPH2 driven tumours

Monoclonal antibody preparation of Golgi phosphoprotein 2 and preliminary application in the early diagnosis of hepatocellular carcinoma

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