Altstock RT, Stein GY, Resau JH, Tsarfaty I. Algorithms for quantitation of protein expression variation in normal versus tumor tissue as a prognostic factor in cancer: Met oncogene expression, and breast cancer as a model. It had been reported that the elevated expression of TNC depended on a malignancy in the tumor stroma of some malignancies, including oral cancer, sarcoma, breast cancer, and colon cancer, squamous cell carcinoma (Hindermann et al., 1999) chondrosarcoma (Ghert et al., 2001), breast cancer (Tsunoda et al., 2003) and colon cancers (Hanamura et al., 1997; Suzuki et al., 2017). Herein, we will discuss some prominent examples of peptides identified through phage display biopanning techniques and their application in the biomedical field. The technology has contributed to the fields of immunotherapy and vaccine development. Moreover, compared to proteins/antibodies, peptides can be generated faster and cheaper and can be stored at room temperature (RT). doi: 10.1128/jvi.00050-23. Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G. HER2 testing in gastric cancer: a practical approach. Hellstrom I, Horn D, Linsley P, Brown JP, Brankovan V, Hellstrom KE. Roushlati and co-workers first described in vivo phage display technology in 1996 (Pasqualini and Ruoslahti, 1996). Out of a total of 35 clones, 19 had the same sequences (denoted peptide #1, FHKHKSPALSPV, 54.2% consensus) and another 13 clones were also identical (denoted peptide #2, FHKPFFPKGSAR, 37.1% consensus). Although the role of NG2 in angiogenesis is still unclear, NG2 is a cell surface receptor for type-VI collagen and also binds to PDGF-A, which could potentially stimulate this growth factor (Nishiyama et al., 1996). In 1988, Parmley and Smith attained a noticeable enhancement of phage display technology by relocating the cloning site of external DNA sequences into another part of the gene coding for. Ebert M, Yokoyama M, Friess H, Buchler MW, Korc M. Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer. However, target-unrelated peptides can often be obtained and cause ambiguous results. Unauthorized use of these marks is strictly prohibited. Phage Display - an overview | ScienceDirect Topics 2D). Multifaceted selection continues to increase our ability to build massive libraries and explore their use in new research areas for phage display. Phage display screening of therapeutic peptide for cancer targeting and The 2018 Nobel Prize in Chemistry: phage display of peptides and antibodies Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping . Giordano et al. . PDF The 2018 Nobel Prize in Chemistry: phage display of peptides and antibodies 2B). Rong S, Jeffers M, Resau JH, Tsarfaty I, Oskarsson M, Vande Woude GF. Pericytes secrete growth factors that stimulate EC proliferation. Mendelsohn J, Baselga J. Mann NH. The 2018 Nobel prize in chemistry: phage display of peptides and antibodies. Phage peptide display is a powerful technique for discovery of various target-specific ligands. The importance of phage display platforms was recognized by awarding the Nobel Prize in 2018 'for the phage display of peptides and antibodies'. Phosphatidylinositol transfer protein, membrane-associated 3 (PITPNM3), also known as Nir1, is essential in CCL18-induced chemotaxis through calcium influx. Article However, the group of Sir Gregory P. Winter was able to present the first reports demonstrating the successful display of the scFv of an antibody on the phage used by Smith (fd-tet phage), the construction of combinatorial scFv phage display antibody libraries, and the possibility to humanize murine antibodies using human antibody scaffolds [17,18,19]. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. When conjugated with TAT peptide, pro-apoptotic peptides (KLAKLAK)2 conjugate was taken up efficiently by mouse melanoma and human breast cancer cells in vitro. Lysine-targeted reversible covalent ligand discovery for proteins via phage display. Phage displayA powerful technique for immunotherapy - PMC Jyothi T. Cancer treatment using peptides: current therapies and future prospects. We previously reported an identification of STAT3-binding peptide (APTSTAT3, Kd ~231 nmol/L). Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Phage display and other peptide display technologies (Journal Article Small molecules such as folic acid (targeting folate receptor ) and mannose (targeting mannose receptor) have been conjugated to drugs or carriers for macrophage targeting and drug delivery (Hashida et al., 2001; Low et al., 2008; Yu et al., 2013). Zhou JC, Soto CM, Chen MS, Bruckman MA, Moore MH, Barry E, et al. Rasanen K, Vaheri A. Activation of fibroblasts in cancer stroma. Xiao J, Burn A, Tolbert TJ. The clinical significance of tenascin-C splice variant expression in chondrosarcoma. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Identification of a met-binding peptide from a phage display library. Various studies have linked the overexpression of this C-Met-ligand-pair to most types of human solid tumors, including brain (Jung et al., 1994), breast (Altstock et al., 2000), ovary (Huntsman et al., 1999), thyroid (Di Renzo et al., 1992), pancreas (Ebert et al., 1994), stomach (Di Renzo et al., 1991), prostate (Humphrey et al., 1995) and nasopharyngeal carcinoma (Qian et al., 2002). Yu D, Hung MC. 1997;97:391410. Phage-display is a powerful technology for screening and isolating target specific peptides. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R. Identification and expansion of human colon-cancer-initiating cells. Clackson T, Hoogenboom HR, Griffiths AD, Winter G. Making antibody fragments using phage display libraries. However, if succeeded in overcoming this barrier, peptides could be much more effective than antibodies or their derivatives due to the absence of thiolated secondary structure, allowing peptides to retain their original secondary structure in exerting the targeting effect. . Various approaches in capturing high affinity peptide through phage display screening. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Indeed, most known applications of phage display are related to the development of therapeutic antibodies, because they have yielded a variety of economical, accurate, and efficient biopharmaceuticals. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and over-expressed receptors on cancer cells identified through phage display screening. PubMed Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. Yu SS, Lau CM, Barham WJ, Onishko HM, Nelson CE, Li H, Smith CA, Yull FE, Duvall CL, Giorgio TD. Clipboard, Search History, and several other advanced features are temporarily unavailable. Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. The novelty of this method lies in the additional step of cell-surface-binding peptides sorting based on differential centrifugation. Although in situ phage display screening using immobilized antigen is capable of generating high affinity and specificity peptide (Kim et al., 2012b), to better mimic cellular and body condition, ample researches are being done on in vitro, in vivo (Liu et al., 2018), ex vivo (Sorensen and Kristensen, 2011) and even in cancer patient (Krag et al., 2006) screening for high affinity peptide in a heterogenous environment as this is a closer representation to their original condition. isolated a peptide that not only selectively bound to TNC in xenograft mouse tissue and patient tumors but also reduced TNC-induced cell rounding and migration. This peptide conjugate also induced apoptosis in the various cancer cell lines such as melanoma, cervical carcinoma, non-small cell lung carcinoma, breast cancer (Yang et al., 2010). CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. However, a short, singular linear ligand, peptides usually lack avidity, that is the ability to bind to the target via multiple interactions that can synergize their binding to enhance the affinity and also lead to enhancement of target residence time resulting in high local concentration of the targeted molecules (Vauquelin and Charlton, 2013). Signaling through the epidermal growth factor receptor during the development of malignancy. Anti-endosialin antibodydrug conjugate: potential in sarcoma and other malignancies. These peptides specifically homed to tumor vasculature in vivo but not to tumor vasculature in NG2 knockout mice, indicating the specificity and targeting capability of these peptides (Burg et al., 1999). 1991;352:6248. Florek M, Haase M, Marzesco AM, Freund D, Ehninger G, Huttner WB, Corbeil D. Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D. Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells. 2C). Importantly, in glioblastoma and colorectal cancer, CD133-expressing cells are considered cancer stem cells (CSCs) as they mediate tumor initiation and metastasis (Singh et al., 2004; OBrien et al., 2007; Ricci-Vitiani et al., 2007). Undoubtedly, work by Winter and co-workers on phage display technology is not only groundbreaking, but also abundant. Phages are extraordinarily robust and stable virus particles, which use bacterial cells as hosts for replication. Receptor targeting for tumor localisation and therapy with radiopeptides. More importantly, peptides have fewer amino acids than proteins/antibodies, thus they are easier to be modified to improve affinity. Ruoslahti E. The RGD story: a personal account. [Google Scholar] 41. This method utilizes bacteriophage to display foreign peptides or antibodies on their surface through insertion of the gene encoding the corresponding polypeptides into the phage genome. Taking advantage of the synergistic three-dimensional structure for optimal binding, APTEDB exhibited a high binding affinity (Kd ~65 nmol/L) to EDB and could be used as a targeting ligand to be conjugated to anti-cancer drugs for high tumor selectivity and reducing systemic toxicity (Kim et al., 2014; Kim et al., 2016), deliver biologics (i.e., oligonucleotides, siRNA and drugs) for solid tumor treatment (Saw et al., 2013; Saw et al., 2015; Saw et al., 2017) and to encapsulate superparamagnetic iron oxide particles for Magnetic Resonance Imaging of EDB over-expressing tumors (Park et al., 2012). Not only APTSTAT3-9R blocked STAT3 phosphorylation, they also reduced the expression of STAT downstream molecules in various types of cancer cells (melanoma, breast, lung, liver and brain cancer) Furthermore, intra-tumoral injection of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft tumor models. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. To screen for novel PSMA-specific peptide to be used as targeting ligands and targeted drug delivery to prostate cancer cells, Jin et al. Inufusa H, Nakamura M, Adachi T, Nakatani Y, Shindo K, Yasutomi M, Matsuura H. Localization of oncofetal and normal fibronectin in colorectal cancer. Using the Roche 454 NGS platform, Lisowska et al. FR is significantly up-regulated in a many cancer such as ovarian cancer (OC), endometrial adenocarcinoma and non-small cell lung cancer (NSCLC) (Kane et al., 1988; Matsue et al., 1992; Kelemen, 2006). PubMed Takayama H, LaRochelle WJ, Sharp R, Otsuka T, Kriebel P, Anver M, Aaronson SA, Merlino G. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. One of the most extensive changes in ECM remodeling is the addition of extra-domain A and B (EDA and EDB), which are alternatively spliced-in during the synthesis of tumor-associated fibronectin. Albrecht M, Renneberg H, Wennemuth G, Moschler O, Janssen M, Aumuller G, Konrad L. Fibronectin in human prostatic cells in vivo and in vitro: expression, distribution, and pathological significance. Design and validation of a specific scavenger receptor class AI binding peptide for targeting the inflammatory atherosclerotic plaque. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. In 1985, George Smith first described phage display by demonstrating the ability of a filamentous phage to display peptide by fusing the library of peptide sequence into the viruss capsid protein (Smith, 1985). WO2016029125A1) for the screening and evaluation of EGFR-targeting peptide through in situ phage display screening, utilizing the PhD-7 heptapeptide random library and PhD-12 decapeptide random library provided by New England Biolab. However, since the invention of phage display of peptides and proteins in the late 1980s and 1990s, the initial use of bacteriophages was boosted from clinical applications, such as identification of ligands, evaluation of proteinprotein interactions, or production of antibodies, to the multiple implementations in which they are used nowadays, including the construction of nanotubes, nanobatteries, or nanorods [3, 4] and, in recent years, for analytical biosensing [5, 6]. Co-localization of LS-7 was seen with CD133+ cells but not CD133- cells. The site is secure. As expected, this prediction was proven in subsequent reports that were seminal contributions to the full development of phage display of peptide libraries [12, 13]. M13 is a commonly used bacteriophage for the display of peptides and antibody fragments and has five coat proteins. Tumor-associated macrophages contribute to tumor progression in ovarian cancer. The antibody molecule is a sizeable bivalent molecule of 150kDa composed of a heavy and a light chain. There is a myriad of targeting ligands that are currently known to be overexpressed in various cancer, differing in cancer types and subtypes, stages of cancer. Interestingly, the selected phage bound to MMP-2 and MMP-9 also specifically homes to tumor vasculature (Koivunen et al., 1999), indicating that (i) that one, or both, of these MMPs is specifically expressed in tumor vasculature and (ii) they are available for phage binding from the circulation. This linear peptide, which has Kd ~11 mol/L binding affinity towards EDB, demonstrated excellent specific targeting to prostate cancer in vivo and could be utilized as an imaging agent for EDB-overexpressing prostate cancer (Han et al., 2015). Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. HER2 genes could be amplified to nearly about 2 million receptors on the surface of tumor cells (Kallioniemi et al., 1992; Gutierrez and Schiff, 2011). Su JL, Lai KP, Chen CA, Yang CY, Chen PS, Chang CC, Chou CH, Hu CL, Kuo ML, Hsieh CY, et al. OBrien CA, Pollett A, Gallinger S, Dick JE. In another study, Han et al. Their sequence, activities and function are summarized in Table2 (Ujula et al., 2010; Ndinguri et al., 2012). Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells. With the advancement of technology, one could now use a combined primary phage display screening and a secondary computational optimization method to develop an optimal peptide for targeting any receptor of interest in the field of solid tumor therapy. Kwon MK, Nam JO, Park RW, Lee BH, Park JY, Byun YR, Kim SY, Kwon IC, Kim IS. Humphrey PA, Zhu X, Zarnegar R, Swanson PE, Ratliff TL, Vollmer RT, Day ML. The second step is the target capturing step, in which the phage library is incubated with target molecule for a specific time to allow binding (Fig. Subsequently, many other publications followed, describing the isolation of tumor vasculature related targeting peptides (Table2) (Landon and Deutscher, 2003; Zurita et al., 2003; Ruoslahti, 2004; Kelly et al., 2005; Su et al., 2005). 2023 . Homogenous in situ screening requires only the specific target to be coated on a 96-well (Fig. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Bhowmick NA, Neilson EG, Moses HL. Optimization of a glucagon-like peptide 1 receptor antagonist antibody for treatment of hyperinsulinism Diabetes. Generating human proteome antibodies via phage display and - UCSF Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment. The opposite situation, when the molecule displayed on phages is an antibody, was made possible owing to a breakthrough step towards the production of in vitro antibodies against any target or the development of therapeutic antibodies. Phage display involves genetically manipulating bacteriophage so that peptides or antibodies can be expressed on their surface (Fig. Ample evidences now show that VEGFR family could be exploited as a potent therapeutic target in cancers. Figure5 highlighted the Top-10 cancer-associated overexpressed receptors and their corresponding publications in PubMed until 2018. The first in-human phage display screening was reported by Arap and colleagues in 2002. Chem Rev. Laakkonen P, Porkka K, Hoffman JA, Ruoslahti E. A tumor-homing peptide with a targeting specificity related to lymphatic vessels. The basics of epithelial-mesenchymal transition. Subsequently, the hybrid coat protein is incorporated into the phage and released from the host cell, so that the foreign peptide or protein is displayed on its surface. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Targeting of the epidermal growth factor receptor with mesoporphyrin IXpeptide conjugates. Cell suspension was first incubated with phage in an aqueous upper phase, which will then be centrifuged through a non-miscible organic lower phase. Nanoscale bacteriophage biosensors beyond phage display. Molecular pathways: next-generation immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Developing a strategy to make antibodies for phosphorylated peptides. Bottom: (a) Description of different antigen presentation methods used to perform the biopanning procedure: (1) direct immobilization (microplates, sensor chips, immunopins, etc. Rouslahti et al. The disadvantages of in situ screening includes the risk of non-specific binding of the isolated peptide when exposed to in vitro or in vivo system. Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, Zabinski RF, Sutherland MK, Gerber HP, Van Orden KL, et al. official website and that any information you provide is encrypted Rong S, Segal S, Anver M, Resau JH, Vande Woude GF. Nishiyama A, Lin XH, Giese N, Heldin CH, Stallcup WB. Chiquet-Ehrismann R. What distinguishes tenascin from fibronectin? eCollection 2019 Jul 31. Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery. In cancer treatment, overexpressed receptors are modulated by targeting agents such as antibodies, antibody fragments, peptides or small chemicals that could block their activities by directly binding these receptors, halting downstream mechanism therefore blocking cancer progression. Google Scholar. Rajotte D, Arap W, Hagedorn M, Koivunen E, Pasqualini R, Ruoslahti E. Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. As a library, NLM provides access to scientific literature. Ghosh S, Sullivan CA, Zerkowski MP, Molinaro AM, Rimm DL, Camp RL, Chung GG. A pH-responsive alpha-helical cell penetrating peptide-mediated liposomal delivery system. Ferrara N, Gerber HP, LeCouter J. Also, in 1991, Winter and co-workers published a report on the phage display of Fab fragments [16] and showed that heterodimeric Fab fragments could be assembled on the surface of the phage by linking one chain to the phage coat protein and secreting the other into the bacterial periplasm. Before Koukourakis MI, Giatromanolaki A, Thorpe PE, Brekken RA, Sivridis E, Kakolyris S, Georgoulias V, Gatter KC, Harris AL. In these manuscripts describing epitope mapping of antibodies, phage display peptide libraries were constructed using the framework for producing the libraries fused to the pIII protein developed by Smith for the selection of binding peptides. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Klein G, Beck S, Muller CA. While current monoclonal antibody therapies targeting CD47/SIRP have demonstrated some anti-tumor effectiveness, there are several inherent limitations associated with these formulations. An official website of the United States government. Li J, Wang H, Li J, Bao J, Wu C. Discovery of a potential HER2 inhibitor from natural products for the treatment of HER2-Positive Breast cancer. Physiologic and clinical implications. Phage display screening of therapeutic peptide for - Home - Springer Matrix metalloproteinases (MMPs) family is among the molecules that are upregulated in tumor microenvironment, and has been known to be functionally important in angiogenesis (Koivunen et al., 1999). Both scFv and Fab antibody formats have been successfully used in antibody libraries displayed on phages [9, 15, 16]. Nevertheless, the process of identifying . In summary, phage display has greatly evolved in the last 25years since the seminal report describing the technology, and its initial expected applications have become multiple (bio) applications with huge revenues. Provided by the Springer Nature SharedIt content-sharing initiative, The 2018 Nobel Prize in Chemistry: phage display of peptides and antibodies, https://doi.org/10.1007/s00216-019-01714-4. In 2012, Segers et al. The biology of VEGF and its receptors. reported a novel peptide that binds selectively to scavenger receptor-A on macrophages in atherosclerotic plaques.
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