In Vivo Phage Display to Identify M Cell-Targeting Ligands

Higgins, Lisa; Lambkin, Imelda; Donnelly, Graham; Byrne, Daragh; Wilson, Carolyn A.; Dee, Jacqueline; Smith, Melanie; O’Mahony, Donagh

doi:10.1023/b:pham.0000022418.80506.9a

Cited by 53 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among them, phage display approaches have shown great potential for isolating antibodies or peptides that recognize specific target molecules, such as vascular endothelial growth factor (22), α v β 3 integrin (23,24), NF-κB (25), and p53 (26,27). Many studies have shown that tissue-specific peptides can be isolated with no prior knowledge of the tissue profile by in vivo phage display technology (28,29). The homing peptides screened by in vivo phage display have revealed an unexpected degree of diversity of blood vessels (30).…”

Section: Discussionmentioning

confidence: 99%

Targeted Drug Delivery to Hepatocarcinoma In vivo by Phage-Displayed Specific Binding Peptide

Han

Wang

et al. 2010

Molecular Cancer Research

View full text Add to dashboard Cite

Hepatocellular carcinoma is one of the deadliest cancers in the world. In this study, a hepatocarcinoma-specific binding peptide, which could be used for drug delivery in targeting therapy, was obtained by in vivo phage display technology. After three rounds of panning, only the potential motif Pro-Ser was found in 80 sequenced phage clones. Phage A54 (sequence AGKGTPSLETTP) was shown to be the most effective and specific to the liver cancer cells by cell-based ELISA in all 130 tested clones. After phage A54 was injected i.v. into the xenograft-bearing mice for in vivo distribution, phage enrichment was found in tumor tissues compared with control phage C10 and normal liver tissues through phage titering and immunohistochemical staining. Next, the specific binding ability of synthesized peptide A54 was further confirmed by fluorescence microscopy, competition binding, and fluorescence-activated cell sorting assay. A54 and A54M (sequence AGKGTAALETTP) were synthesized and coupled to doxorubicin (DOX) to do the preliminary targeting therapy. After the treatment, the proliferation of liver cancer cells treated with A54-DOX was restrained significantly in vitro when compared with A54M-DOX-treated group. Reduction in tumor size and prolongation of long-term survival were also found in xenograft-bearing models compared with free DOX-treated group. In conclusion, the specific binding peptide A54, which was screened from phage display library, represents a promising approach for the development of novel target therapy strategies against hepatocellular carcinoma. Mol Cancer Res; 8(2); 135-44. ©2010 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeted Drug Delivery to Hepatocarcinoma In vivo by Phage-Displayed Specific Binding Peptide

Han

Wang

et al. 2010

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…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%

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

“…In addition, ligands targeting human papillomavirus, which were selected through biopanning against human papillomavirus 16-transformed SiHa cells, could deliver cargo molecules to the target cells (29). Moreover, ligands against PPs, the gut epithelium, or polymeric IgRs for vaccine or drug delivery into the mucosal area were isolated using a biopanning approach, although the efficiency of Ag delivery was tested only in an in vitro cell culture system (30)(31)(32). In a previous study, we showed that oral vaccination using the GM1 ganglioside-targeting ligand, which was selected from panning of a phage display library, induced increased mucosal and systemic immune responses against a ligand-fused Ag (33).…”

mentioning

confidence: 99%

The M Cell-Targeting Ligand Promotes Antigen Delivery and Induces Antigen-Specific Immune Responses in Mucosal Vaccination

Kim¹,

Seo²,

Kim³

et al. 2010

The Journal of Immunology

114

100

View full text Add to dashboard Cite

Oral mucosal immunization can induce protective immunity in both systemic compartments and the mucosa. Successful mucosal immunization depends on Ag delivery to the mucosal immune induction site. The high transcytotic activity of M cells within the mucosa makes these cells attractive targets for mucosal Ag delivery, although it remains unclear whether delivery of Ag to M cells only can guarantee the induction of effective immune responses. In this study, we evaluated the ability of an M cell-targeting ligand with adjuvant activity to induce immunity against ligand-fused Ag. We selected M cell-targeting ligands through biopanning of a phage display library against differentiated in vitro M-like cells and produced the recombinant Ags fused to the selected ligands using the model Ag. One of the selected peptide ligands, Co1, promoted the binding of ligand-fused Ag to mouse Peyer’s patch M cells and human M-like cells that had been defined by binding with the M cell-specific and anti-GP2 Abs. In addition, Co1 ligand enhanced the uptake of fused Ag by immunogenic tissue in an ex vivo loop assay and in vivo oral administration experiments. After oral administration, the ligand-fused Ag enhanced immune responses against the fused Ag compared with those of the control Ag without ligand. In addition, this use of the ligand supported a skewed Th2-type immune response against the fused Ag. Collectively, these results suggest that the ligand selected through biopanning against cultured M-like cells could be used as an adjuvant for targeted Ag delivery into the mucosal immune system to enhance immune induction.

show abstract

In Vivo Phage Display to Identify M Cell-Targeting Ligands

Abstract: In summary, we have identified novel ligands that target M cells and Peyer's patch tissue, and thus may have utility in the targeted oral delivery of vaccines and vaccine carrier systems to the mucosal immune system within the gastrointestinal tract.

Cited by 53 publications

References 40 publications

Targeted Drug Delivery to Hepatocarcinoma In vivo by Phage-Displayed Specific Binding Peptide

Targeted Drug Delivery to Hepatocarcinoma In vivo by Phage-Displayed Specific Binding Peptide

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

The M Cell-Targeting Ligand Promotes Antigen Delivery and Induces Antigen-Specific Immune Responses in Mucosal Vaccination

Contact Info

Product

Resources

About