In Vivo Phage Display Selection in the Human/SCID Mouse Chimera Model for Defining Synovial Specific Determinants

Lee, Lewis; Garrood, Toby; Pitzalis, Costantino

doi:10.1007/978-1-59745-402-5_26

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Similarly, vaccines elicit quantitatively and qualitatively different immune responses depending on the route of application. For example, gastrointestinal administration of proteins, in the absence of adjuvants, preferentially induces immunological tolerance ("oral tolerance") 1 , but adjuvant-including enteric vaccines are superior in inducing IgA responses which are important to prevent infections with 4 targeting [13][14][15] and receptor identification 16,17 . Extensive screening of phage display libraries has also been used to identify ligands that facilitate translocation across the mucosa of the gastrointestinal tract 18 or binding to and transport via M cells 19,20 or goblet cells 21,22 .…”

Section: Introductionmentioning

confidence: 99%

“…Phage display technology has been widely used for in vitro and in vivo screening of tissue-specific markers and peptides . The method has been successfully employed to dissect biological processes, such as homing to vascular tissue in tumors, − cancer metastasis, ,− synovial targeting, − and receptor identification. , Extensive screening of phage display libraries has also been used to identify ligands that facilitate translocation across the mucosa of the gastrointestinal tract or binding to and transport via M cells , or goblet cells. , …”

Section: Introductionmentioning

confidence: 99%

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Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

et al. 2015

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In this study we identified and characterized a novel cyclic peptide that facilitates the rapid transportation of conjugated molecules across the epithelial layer of the small intestine. The peptide was initially selected from phage display libraries using a large animal experimental model which employed consecutive in vitro and in vivo panning. The procedure was designed to enrich for peptides that facilitated transcytosis across the intestinal epithelium into the intestinal afferent lymphatic system. A small set of peptides was repeatedly isolated using this selection method, 2 however the cyclic nonamer CTANSSAQC, 13C dominated. The activity of the putative targeting peptide C13 was then verified using a mouse model. These experiments showed that the 13C peptide as well as macromolecules conjugated to it were rapidly transported across the intestinal mucosa into distinct subsets of epithelial cells and CD11+ cells located in the lamina propria and Peyer's Patches. Significant amounts of intact protein could be delivered into the systemic circulation after rectal and nasal application. Thus, peptide 13C is regarded as an attractive carrier candidate for mucosal delivery of large molecules. The preferential targeting to distinct intestinal cells may be utilized to deliver active biological drugs for the effective control of diseases of the gut.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

et al. 2015

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“…After tumors reached 7 to 8 mm in diameter, we injected the phage library (1×10 13 CFU) dissolved in 100 µl saline into the tail veins of tumor-bearing mice. After 15 min, the animals were sacrificed by an overdose of anesthetic and perfused via the heart with 100 ml of PBS [15]. Next, the tumor tissue was snap-frozen in liquid nitrogen and homogenized in a mortar.…”

Section: Methodsmentioning

confidence: 99%

Serum Anti-BPAG1 Auto-Antibody Is a Novel Marker for Human Melanoma

et al. 2010

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Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1) as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP) and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361) and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01). Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

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