<i>In situ</i> antibody phage display yields optimal inhibitors of integrin α11/β1

Gallo, Eugenio; Kelil, Abdellali; Bayliss, Peter E.; Jeganathan, Ajitha; Egorova, O. I.; Ploder, Lynda; Adams, Jarrett; Giblin, Patricia; Sidhu, Sachdev S.

doi:10.1080/19420862.2020.1717265

Cited by 14 publications

(15 citation statements)

References 52 publications

(53 reference statements)

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“…Other examples include the LS-7 (LQNAPRS) peptide which targets the CSC-associated marker CD133 [ 122 ] and the new nanobody VUN100 for targeting the G-protein coupled receptor homolog US28 that is found to be overexpressed in glioblastoma [ 123 ]. Antibodies with inhibitory activity towards integrin α11/β1 were also identified in situ [ 124 ]. Recently, in vitro phage display using gastric cancer cells allowed the identification of DE532 (VETSQYFRGTLS) and GP-5 (IHKDKNAPSLVP) peptides, and specific antibodies to target gastric cancer [ 125 ].…”

Section: Targeting Approaches In the Context Of Cancermentioning

confidence: 99%

Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

et al. 2020

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Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers.

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Section: Targeting Approaches In the Context Of Cancermentioning

confidence: 99%

Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

et al. 2020

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“…Integrin α11/β1, a marker of aggressive tumors that indirectly stimulate cancer-stromal stiffness and tumor progression, may be an attractive target for anti-cancer therapeutic antibodies. Gallo successfully selected functional antibodies that competed with collagen-I for binding to Integrin α11/β1 to inhibit cell adhesion by in situ antibody phage display (Gallo et al 2020 ). CD44, a cancer-associated membrane glycoprotein involved in cell adhesion, tumor progression and drug-resistance, is a potential diagnostic target for cancer detection.…”

Section: Potential Applications Of Targeting Peptidesmentioning

confidence: 99%

Application of Phage-Displayed Peptides in Tumor Imaging Diagnosis and Targeting Therapy

Xü

et al. 2020

Int J Pept Res Ther

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Phage display is an effective and powerful technique that provides a route to discovery unique peptides targeting to tumor cells. Specifically binding peptides are considered as the valuable target directing molecule fragments with potential efficiency to improve the current tumor clinic, and offer new approaches for tumor prevention, diagnosis and treatment. We focus on the recent advances in the isolation of tumor-targeting peptides by biopanning methods, with particular emphasis on molecular imaging, and pharmaceutical targeting therapy.

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“…First, Library F is extremely diverse (> 10 10 unique members) and precisely designed to ensure that most members are stable and well-displayed on phage 38 . Second, the library proves functional for selections with either puri ed antigens 37 or cell-surface antigens 36 and has yielded numerous selective Abs per selections 36 .…”

Section: Cell-based In Situ Selection For Anti-cd151 Absmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Recently, we reported optimized methods for in situ selections with phage-displayed synthetic antibody libraries with native antigen on live cells to develop a large panel of selective antibodies for integrin-α11/ β1, a marker of aggressive tumors that is involved in stroma-tumor crosstalk 36 . Manual screening of over one thousand phage clones identi ed unique Abs with strong and selective binding to cells expressing integrin-α11/β1, and notably, most of these Abs did not recognize the puri ed antigen, suggesting that cell-based selections were essential for targeting native epitopes 36 . Moreover, next generation sequencing (NGS) analysis of the abundance of unique clones in the selection pools showed that most of the Abs identi ed by clonal screening were among the most abundant and enriched amongst the NGS sequences, but intriguingly, many other sequences were also identi ed, suggesting that clonal screening had only isolated a small subset of antigen-speci c clones 36 .…”

Section: Introductionmentioning

confidence: 99%

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CellectSeq: In Silico Discovery of Antibodies Targeting Integral Membrane Proteins Combining In Situ Selections of Phage Displayed Synthetic Antibodies and Next-Generation Sequencing

Kelil¹,

Gallo²,

Adams³

et al. 2020

Preprint

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Synthetic antibody (Ab) technologies are efficient and cost-effective platforms for the generation of monoclonal proteomic tools against human antigens. Yet, they typically depend on purified proteins, which exclude from interrogation integral membrane proteins that require the lipid bilayers to support their native form or function. Here, we present a novel Ab discovery strategy, termed CellectSeq, for targeting integral membrane proteins presented on native cells in complex environment. As proof of concept, we targeted the challenging tetraspanin receptor CD151, a target linked to cancer. First, we optimized in situ cell-based selections to enrich Ab pools for antigen-specific binders. Then, we designed novel NGS procedures to explore Ab pools diversities and abundances with enhanced accuracies. Finally, we developed novel motif-based scoring and error filtering algorithms for the comprehensive interrogation of NGS data to identify Abs with high diversities and specificities, even at extremely low abundances. We identified highly selective and diversified Abs against CD151 with abundance as low as 0.00009% for which manual sampling or identification using Abs abundances in NGS data would have been impossible. Here we show that CellectSeq enables the rapid discovery of diversified and selective antibodies against CD151, with implications for other integral membrane proteins and cell-surface receptors.

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In situ antibody phage display yields optimal inhibitors of integrin α11/β1

Cited by 14 publications

References 52 publications

Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

Application of Phage-Displayed Peptides in Tumor Imaging Diagnosis and Targeting Therapy

CellectSeq: In Silico Discovery of Antibodies Targeting Integral Membrane Proteins Combining In Situ Selections of Phage Displayed Synthetic Antibodies and Next-Generation Sequencing

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