Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro(650 views) Foca G, Iaccarino E, Foca A, Sanguigno L, Untiveros G, Cuevas-nunez M, Strizzi L, Leonardi A, Ruvo M, Sandomenico A
Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy., Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy., Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA., Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA; College of Dental Medicine, Dwners Grove, Chicago, IL, USA., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy. Electronic address: menotti.ruvo@unina.it., Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR), Naples, Italy. Electronic address: annamaria.sandomenico@cnr.it.,
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
Midwestern University, Colleges of Graduate Studies, Dwners Grove, Chicago, IL, USA.
College of Dental Medicine, Dwners Grove, Chicago, IL, USA.
References: Not available.
Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro
Human Cripto-1 (Cripto-1), the founding member of the EGF-CFC superfamily, is a key regulator of many processes during embryonic development and oncogenesis. Cripto-1 is barely present or even absent in normal adult tissues while it is aberrantly re-expressed in various tumors. Blockade of the CFC domain-mediated Cripto-1 functions is acknowledged as a promising therapeutic intervention point to inhibit the tumorigenic activity of the protein. In this work, we report the generation and characterization of murine monoclonal antibodies raised against the synthetic folded CFC [112-150] domain of the human protein. Through subtractive ELISA assays clones were screened for the ability to specifically recognize "hot spot" residues on the CFC domain, which are crucial for the interaction with Activin Type I receptor (ALK4) and GRP78. On selected antibodies, SPR and epitope mapping studies have confirmed their specificity and have revealed that recognition occurs only on a conformational epitope. Furthermore, FACS analyses have confirmed the ability of 1B4 antibody to recognize the membrane-anchored and soluble native Cripto-1 protein in a panel of human cancer cells. Finally, we have evaluated its functional effects through in vitro cellular signaling assays and cell cycle analysis. These findings suggest that the selected anti-CFC mAbs have the potential to neutralize the protein oncogenic activity and may be used as theranostic molecules suitable as tumor homing agents for Cripto-1-overexpressing cancer cells and tissues and to overcome drug-resistance in routine cancer therapies.
Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro
Ciccarelli M, Sorriento D, Coscioni E, Iaccarino G, Santulli G * Adrenergic Receptors(332 views) Endocrinol Of The Heart In Health And Dis (ISSN: 9780-1280311249780128031117), 2016; N/D: 285-315. Impact Factor:0 ViewExport to BibTeXExport to EndNote
Bogdanovich S, Kim Y, Mizutani T, Yasuma R, Tudisco L, Cicatiello V, Bastos-carvalho A, Kerur N, Hirano Y, Baffi JZ, Tarallo V, Li S, Yasuma T, Arpitha P, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ruvo M, Sandomenico A, Nozaki M, Ijima R, Kaneko H, Ogura Y, Terasaki H, Ambati BK, Leusen JH, Langdon WY, Clark MR, Armour KL, Bruhns P, Verbeek JS, Gelfand BD, De Falco S, Ambati J * Human IgG1 antibodies suppress angiogenesis in a target-independent manner(652 views) Signal Transduct Target Ther (ISSN: 2059-3635print), 2016; 1: N/D-N/D. Impact Factor:0 ViewExport to BibTeXExport to EndNote
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(591 views) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 ViewExport to BibTeXExport to EndNote
Testino G, Leone S, Fagoonee S, Del Bas JM, Rodriguez B, Puiggros F, Marine S, Rodriguez MA, Morina D, Armengol L, Caimari A, Arola L, Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-gentilucci U, Cavallo MG, Morini S, Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV, Lee SM, Jun DW, Cho YK, Jang KS, Kucukazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, Aktas B, Akin KO, Agladioglu K, Ure OS, Topal F, Nazligul Y, Beyan E, Ertugrul DT, Catena C, Cosma C, Camozzi V, Plebani M, Ermani M, Sechi LA, Fallo F, Goto Y, Ray MB, Mendenhall CL, French SW, Gartside PS Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease(697 views) Hepatology (ISSN: 1827-1669electronic, 0026-4806linking), 1988 Sep; 83120693611123109(5): 1019-1026. Impact Factor:0.913 ViewExport to BibTeXExport to EndNote