1997

DOI: 10.1002/(sici)1097-0142(19971215)80:12+<2378::aid-cncr7>3.0.co;2-7

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Tumor targeting potential of the monoclonal antibody BC-1 against oncofetal fibronectin in nude mice bearing human tumor implants

Giuliano Mariani¹,

et al.

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Fn Fragments As Delivery Vehicles1

Nir Cyanine Dyes1

Article1

Pro-angiogenic Factors1

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1997

1997

2023

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Cited by 45 publications

(29 citation statements)

References 15 publications

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“…8,24,50 However, the BC-1 antibody does not directly recognize the human EDB domain, but rather an epitope that is localized on the adjacent type-III repeat 7, which is cryptic in the absence of EDB, but becomes unmasked in B-FN. 23 BC-1 dose not crossreact with murine B-FN, but has successfully been used in biodistribution experiments in mice bearing subcutaneously grafted human tumors 51 and for the imaging of patients with cancer. 52 Several groups have tried raising monoclonal antibodies to EDB using hybridoma technology, without success until now, possibly because of the identity of the EDB sequence from mouse to man.…”

Section: Fn Fragments As Delivery Vehiclesmentioning

confidence: 93%

Fibronectin as target for tumor therapy

¹

,

²

,

³

2005

Int. J. Cancer

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During cancer progression, the extracellular matrix (ECM) of the tissue in which the tumor grows is extensively remodeled, both by degradation of preexisting ECM molecules and by the neosynthesis of ECM components, which in many cases are not present in the ECM of normal tissues. Fibronectin (FN), a class of highmolecular-weight adhesive glycoproteins, plays a prominent role in mediating ECM function, because of its high abundance and its interaction with cellular components. Furthermore, the generation of tumor-associated FN isoforms allows the development of specific ligands (e.g., antibodies), which can be used for the selective delivery of therapeutic agents to the tumor environment. In view of these considerations, it is not surprising that FN is being used as a target for biomolecular intervention, both for the development of inhibitory molecules that block the interaction of FN with integrins and other receptors on the cell surface, and for the development of ligand-based targeted imaging and therapeutic strategies. In this review, we briefly present the essential properties of FN, and we then focus on the therapeutic strategies that are currently in preclinical or clinical development and feature FN as a target, or that are based on FN fragments so as to promote tumor-growth inhibition. ' 2005 Wiley-Liss, Inc.Key words: fibronectin; ECM; angiogenesis; EDB; vascular tumor targeting Tumor-associated extracellular matrix components Neoplastic cells are obviously the most important component of solid tumors, and it is not surprising that most efforts in cancer research focus on the characterization of the properties of tumor cells and of their molecules. However, the role of the tumor stroma (and in particular of its extracellular matrix (ECM) components) is becoming increasingly recognized as an important determinant for the growth and progression of solid tumors.1,2 The extensive remodeling of the normal ECM in tumors proceeds through 2 main processes: (i) degradation of preexisting ECM molecules by a number of hydrolytic enzymes (e.g., proteases) that are produced, activated and/or induced by neoplastic cells, and (ii) neosynthesis of ECM components, which in many cases, are not present (or present at low concentration) in the normal tissues. This tumor ECM may generate a more suitable and possibly more permissive and/or instructive environment for tumor growth and progression. Furthermore, tumor-associated ECM components, which may be produced by tumor cells, stromal cells and/or endothelial cells, often represent ideal targets for biomolecular intervention, as will be illustrated in this review. ECM tumor antigens are in general more abundant and possibly more stable than tumor-associated antigens of the tumor cell surface, thus facilitating tumor imaging and targeted therapeutic applications.Among the most abundant ECM components (such as collagens, tenascins, proteoglycans, glycosaminoglycans and laminin), 1 fibronectins (FNs) play a special role both in terms of their functional properties and becau...

“…8,24,50 However, the BC-1 antibody does not directly recognize the human EDB domain, but rather an epitope that is localized on the adjacent type-III repeat 7, which is cryptic in the absence of EDB, but becomes unmasked in B-FN. 23 BC-1 dose not crossreact with murine B-FN, but has successfully been used in biodistribution experiments in mice bearing subcutaneously grafted human tumors 51 and for the imaging of patients with cancer. 52 Several groups have tried raising monoclonal antibodies to EDB using hybridoma technology, without success until now, possibly because of the identity of the EDB sequence from mouse to man.…”

Section: Fn Fragments As Delivery Vehiclesmentioning

confidence: 93%

Fibronectin as target for tumor therapy

¹

,

²

,

³

2005

Int. J. Cancer

Self Cite

View full text Add to dashboard Cite

During cancer progression, the extracellular matrix (ECM) of the tissue in which the tumor grows is extensively remodeled, both by degradation of preexisting ECM molecules and by the neosynthesis of ECM components, which in many cases are not present in the ECM of normal tissues. Fibronectin (FN), a class of highmolecular-weight adhesive glycoproteins, plays a prominent role in mediating ECM function, because of its high abundance and its interaction with cellular components. Furthermore, the generation of tumor-associated FN isoforms allows the development of specific ligands (e.g., antibodies), which can be used for the selective delivery of therapeutic agents to the tumor environment. In view of these considerations, it is not surprising that FN is being used as a target for biomolecular intervention, both for the development of inhibitory molecules that block the interaction of FN with integrins and other receptors on the cell surface, and for the development of ligand-based targeted imaging and therapeutic strategies. In this review, we briefly present the essential properties of FN, and we then focus on the therapeutic strategies that are currently in preclinical or clinical development and feature FN as a target, or that are based on FN fragments so as to promote tumor-growth inhibition. ' 2005 Wiley-Liss, Inc.Key words: fibronectin; ECM; angiogenesis; EDB; vascular tumor targeting Tumor-associated extracellular matrix components Neoplastic cells are obviously the most important component of solid tumors, and it is not surprising that most efforts in cancer research focus on the characterization of the properties of tumor cells and of their molecules. However, the role of the tumor stroma (and in particular of its extracellular matrix (ECM) components) is becoming increasingly recognized as an important determinant for the growth and progression of solid tumors.1,2 The extensive remodeling of the normal ECM in tumors proceeds through 2 main processes: (i) degradation of preexisting ECM molecules by a number of hydrolytic enzymes (e.g., proteases) that are produced, activated and/or induced by neoplastic cells, and (ii) neosynthesis of ECM components, which in many cases, are not present (or present at low concentration) in the normal tissues. This tumor ECM may generate a more suitable and possibly more permissive and/or instructive environment for tumor growth and progression. Furthermore, tumor-associated ECM components, which may be produced by tumor cells, stromal cells and/or endothelial cells, often represent ideal targets for biomolecular intervention, as will be illustrated in this review. ECM tumor antigens are in general more abundant and possibly more stable than tumor-associated antigens of the tumor cell surface, thus facilitating tumor imaging and targeted therapeutic applications.Among the most abundant ECM components (such as collagens, tenascins, proteoglycans, glycosaminoglycans and laminin), 1 fibronectins (FNs) play a special role both in terms of their functional properties and becau...

“…In parallel, S. achilefu (then at Mallinckrodt, Inc.) developed cypate, an activatable analog of Icg, with almost identical optical properties to Icg (molar absorptivity, quantum yield) [49]. Other reactive NIr dyes followed [52], and the imaging using the dyes of conjugated to antibodies and small peptides has been demonstrated in vivo in mouse models [53]. These functionalizable NIr dyes have later become the dyes of choice for labeling many types of nanoparticles.…”

Section: Nir Cyanine Dyesmentioning

confidence: 99%

Historical Perspective on Nanoparticles in Imaging from 1895 to 2000

¹

2014

Nanotechnology for Biomedical Imaging and Diagnostics

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“…We then investigated the kinetics of entry of mAbs into the tumors using an in vivo imaging system with near-infrared fluorescence, which can provide deep tissue imaging with high fidelity. 21,22 Anti-CD20 mAb (rituximab), which is specific to human B cell lymphoma but not to carcinoma, was used as a nonspecific control because of its high specificity with less background. 11,23 Until day 3, all mAbs labeled with a near-infrared fluorescence dye including the control mAb were delivered to and retained in both PSN1 tumors, and SUIT2 tumors, indicating passive targeting by the EPR effect ( Figure 3B).…”

Section: Articlementioning

confidence: 99%

Cancer-Stroma Targeting Therapy by Cytotoxic Immunoconjugate Bound to the Collagen 4 Network in the Tumor Tissue

¹

,

²

,

³

et al. 2011

Bioconjugate Chem.

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Some cytotoxic immunoconjugates have been approved for malignant lymphoma, a representative of hypervascular and stroma-poor tumors. However, many human solid tumors possess abundant intercellular stromata that prevent diffusion of cancer cell-specific monoclonal antibodies (mAb) and become a barrier preventing immunoconjugates from directly attacking cancer cells. Here we show the successful development of a new strategy that overcomes this drawback and achieves a highly localized concentration of a topoisomerase I inhibitor, SN 38, by conjugating it via an ester bond to a mAb targeted against collagen 4, a plentiful component of the tumor stroma. Poly(ethylene glycol) (PEG) was utilized as a spacer, close to each bond, to maintain stability in the blood. Immunoconjugates selectively extravasated from leaky tumor vessels and minimally from normal vessels because the immunoconjugates are too large to pass through normal vessel walls. Stroma-targeting immunoconjugates bound to the stroma to create a scaffold, from which sustained release of cytotoxic agent occurred and the agent subsequently diffused throughout the tumor tissue to damage both tumor cells and vessels. Cancer-stroma-targeting immunoconjugate therapy was thus validated as a new modality of oncological therapy, especially for refractory, stromal-rich cancers.

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