Vaccination against the extra domain‐B of fibronectin as a novel tumor therapy

Huijbers, Elisabeth J. M.; Ringvall, Maria; Femel, Julia; Kalamajski, Sebastian; Lukinius, Agneta; Åbrink, Magnus; Hellman, Lars; Olsson, Anna‐Karin

doi:10.1096/fj.10-163022

Cited by 44 publications

(44 citation statements)

References 30 publications

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“…SEPT9 is homologous to septin-2, which is upregulated in cytoskeletal and immune function-related proteome profiles [54]. IFNGR2 is a four-domain fibronectin fragment, which plays a role in autoimmune diseases [55]. CSF3 is in PDB, and is related to immune system functions [56].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery

Ishida¹,

Umeyama²,

Iwadate³

et al. 2013

PPL

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Autoimmune diseases are often intractable because their causes are unknown. Identifying which genes contribute to these diseases may allow us to understand the pathogenesis, but it is difficult to determine which genes contribute to disease. Recently, epigenetic information has been considered to activate/deactivate disease-related genes. Thus, it may also be useful to study epigenetic information that differs between healthy controls and patients with autoimmune disease. Among several types of epigenetic information, promoter methylation is believed to be one of the most important factors. Here, we propose that principal component analysis is useful to identify specific gene promoters that are differently methylated between the normal healthy controls and patients with autoimmune disease. Full Automatic Modeling System (FAMS) was used to predict the three-dimensional structures of selected proteins and successfully inferred relatively confident structures. Several possibilities of the application to the drug discovery based on obtained structures are discussed.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery

Ishida¹,

Umeyama²,

Iwadate³

et al. 2013

PPL

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“…As important cancer markers in tumor ECM, EDA and EDB domains have been used as targets for cancer vaccination. A vaccine was developed against EDB-FN, which elicited production of anti-EDB antibodies and resulted in a 70% tumor volume reduction in T241 fibrosarcoma tumor model 146 . Vaccination against EDA showed that it could attenuate the progression of metastatic breast cancer 147 .…”

Section: Targeting Fibronectin In Cancer Therapymentioning

confidence: 99%

Targeting fibronectin for cancer imaging and therapy

2017

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During cancer progression, the extracellular matrix (ECM) undergoes dramatic changes, which promote cancer cell migration and invasion. In the remodeled tumor ECM, fibronectin (FN) level is upregulated to assist tumor growth, progression, and invasion. FN serves as a central organizer of ECM molecules and mediates the crosstalk between the tumor microenvironment and cancer cells. Its upregulation is correlated with angiogenesis, cancer progression, metastasis, and drug resistance. A number of FN-targeting ligands have been developed for cancer imaging and therapy. Thus far, FN-targeting imaging agents have been tested for nuclear imaging, MRI, and fluorescence imaging, for tumor detection and localization. FN-targeting therapeutics, including nuclear medicine, chemotherapy drugs, cytokines, and photothermal moieties, were also developed in cancer therapy. Because of the prevalence of FN overexpression in cancer, FN targeting imaging agents and therapeutics have the promise of broad applications in the diagnosis, treatment, and image-guided interventions of many types of cancers. This review will summarize current understanding on the role of FN in cancer, discuss the design and development of FN-targeting agents, and highlight the applications of these FN-targeting agents in cancer imaging and therapy.

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“…Applied together with a potent adjuvant cocktail, the immune system recognizes the modified self protein as non self leading to antibody production against the selected target protein. Such a therapeutic vaccine has been developed to target extradomain B of fibronectin (FN-EDB) or extradomain A of fibronectin (FN-EDA) and has shown antitumor activities in an in vivo fibrosarcoma tumor model 57 and in the MMTV-PyMT mouse model of breast cancer. 58 Vaccination of mice and rabbits against the C-domain of tenascin-C induced high serum titers of specific antibodies to the target 59 but its effect in preclinical cancer models is not yet reported.…”

Section: Anti-cancer Immunity and Cancer Immunotherapymentioning

confidence: 99%