A Fibrin-Specific Monoclonal Antibody from a Designed Phage Display Library Inhibits Clot Formation and Localizes to Tumors In Vivo

Putelli, Alessia; Kiefer, Jonathan D.; Zadory, Matthias; Matasci, Mattia; Neri, Dario

doi:10.1016/j.jmb.2014.07.023

Cited by 17 publications

(16 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although several anti-fibrin antibodies have been developed, some of them delay or inhibit fibrin gel formation in the presence of an anti-fibrin antibody, and these have been reported in previous studies 39 40 . Because the disruption of fibrin gel formation can lead to serious adverse effects, we examined the influence of 102-10 Fab on blood coagulation.…”

Section: Resultsmentioning

confidence: 96%

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Obonai

Fuchigami

Furuya

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

show abstract

Section: Resultsmentioning

confidence: 96%

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Obonai

Fuchigami

Furuya

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Human single-chain antibody fragment Tomlinson I and J libraries were panned against non-cross-linked fibrin [21] and only one clone (E4) was identified that, in ELISA, showed a weak preferential binding to fibrin in comparison to fibrinogen. Monoclonal antibody AP2 was selected by phage display from a combinatorial library targeted to N-terminal peptide of α-chain of fibrin [22]. This antibody recognizes five N-terminal amino acids from fibrin and does not react with fibrinogen.…”

Section: Introductionmentioning

confidence: 99%

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

et al. 2019

View full text Add to dashboard Cite

Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the Bβ chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics.

show abstract

“…In particular, phage‐displayed biopanning is a useful methodology for the identification of targeting ligands such as H6, SP2, CREKA, and CLT‐1 for fibrin. The H6 sdFvs recognition motif for fibrin was recently utilized to produce platelet‐like microparticles that act as strong artificial hemostatic agents to enhance clot stability for the treatment of severe haemorrhage .…”

Section: Fibrin As An Artificial Extracellular Matrixmentioning

confidence: 99%

Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

Roberts

Bukhary

Leon‐Valdivieso

et al. 2019

Macromolecular Bioscience

View full text Add to dashboard Cite

This review focuses on fibrin, starting from biological mechanisms (its production from fibrinogen and its enzymatic degradation), through its use as a medical device and as a biomaterial, and finally discussing the techniques used to add biological functions and/or improve its mechanical performance through its molecular engineering. Fibrin is a material of biological (human, and even patient's own) origin, injectable, adhesive, and remodellable by cells; further, it is nature's most common choice for an in situ forming, provisional matrix. Its widespread use in the clinic and in research is therefore completely unsurprising. There are, however, areas where its biomedical performance can be improved, namely achieving a better control over mechanical properties (and possibly higher modulus), slowing down degradation or incorporating cell-instructive functions (e.g., controlled delivery of growth factors).

show abstract

A Fibrin-Specific Monoclonal Antibody from a Designed Phage Display Library Inhibits Clot Formation and Localizes to Tumors In Vivo

Cited by 17 publications

References 52 publications

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

Contact Info

Product

Resources

About