Abstract
Pritumumab, a natural human IgG1kappa mAb, was isolated from the regional lymph node of a patient with cervical cancer. This antibody has been reported to bind the cytoskeletal protein vimentin, and to cell surface expressed vimentin referred to as ecto-domain vimentin (EDV). Here, we report details of the development of a potency of binding assay for pritumumab as a prerequisite before pursuing clinical trials. The enzyme linked immunosorbent assay (ELISA) to detect antibody-binding antigen can serve as a potency assay for release of manufactured samples to be used in clinical studies. Several layers of controls for this assay along with suitability testing for reagents and components of the assay must be developed before the assay can be incorporated for stability testing and release of manufatured samples.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Glassy MC, Handley HH, Hagiwara H, Royston I (1983) UC 729-6, a human lymphoblastoid B cell line useful for generating antibody secreting human-human hybridomas. Proc Natl Acad Sci U S A 80:6327–6331
Glassy MC, Hagiwara H (2009) Summary analysis of the pre-clinical and clinical results of brain tumor patients treated with pritumumab. Hum Antibodies 18:127–137
Babic I, Nurmammadov E, Yenugonda V, Juarez T, Nomura N, Pingle SC, MC G, Kesari S (2017) Pritumumab, the first therapeutic antibody for glioma patients. Hum Antibodies 26:95–101
Glassy MC, Gupta R (2013) Technical and ethical limitations in making human monoclonal antibodies, chapter 2. In: Steinitz M (ed) Springer protocols, Methods in molecular biology, vol 1060. Humana Press, New York, pp 9–30
Glassy MC, McKnight ME (1993) A novel drug discovery programme utilizing the human immune response. Curr Opin Investig Drugs 2:853–858
Glassy MC, McKnight ME (1994) Pharming the human lymph node. Expert Opin Investig Drugs 3:1057
Gupta R, York D, Kotlan B, Bleck G, Glassy E, Glassy M (2013) Use of the Gpex® system to increase production of Pritumumab in a CHO cell line. J Bioprocess Technol Photon 98:318–326
Aotsuka Y, Hagiwara H (1988) Identification of a malignant cell associated antigen recognized by a human monoclonal antibody. Eur J Cancer 24(5):829–838
Kokunai T, Tamaki N, Matsumoto S (1990) Antigen related to cell proliferation in malignant gliomas recognized by a human monoclonal antibody. J Neurosurg 73(6):901–908
Hagiwara H, Aotsuka Y, Yamamoto Y, Miyahara J, Mitoh Y (2001) Determination of the antigen/epitope that is recognized by human monoclonal antibody CLN-IgG. Hum Antibodies 10:77–82
AV H, Glassy MC (2017) Idiotypic antibody network regarding malignant cell regression in the brain tumor patients treated with the natural human monoclonal antibody, Pritumumab. Integr Canc Biol Res 1:003
Kokunai T (2002) Anti-TA226 human monoclonal antibody (ACA-11) against glioma. Nihon Rinsho 60(1):100–106
Fuchs E, Weber K (1994) Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem 63:345–382
Ivaska J, Pallari HM, Nevo J, Eriksson JE (2007) Novel functions of vimentin in cell adhesion, migration, and signaling. Exp Cell Res 313:2050–2062
Chernyatina AA, Nicolet S, Aebi U, Hermann H, Strelkov SK (2012) Atomic structure of the vimentin central a-helical domain and its implications for intermediate filament assembly. Proc Natl Acad Sci 109:13620–13625
Apostolou E, Hochdlinger K (2013) Chromatin dynamics during cellular reprogramming. Nature 502:462–469
Franke WW, Franke WW, Appelhans B, Schmid E, Freudenstein C, Osborn M, Weber K (1979) Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin. Differentiation 15(1):7–25
Mendez MG, Kojima S, Goldman RD (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24(6):1838–1851
Lang SH, Hyde C, Reid IN, Hitchcock IS, Hart CA, Gordon Bryden AA, Villette JM, Stower MJ, Maitiand NJ (2002) Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma. Prostate 52(4):253–263
Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW (2007) Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cell Physiol 213(2):374–383
Mitra A, Satelli A, Xia XQ, Xia CJ, Mishra L, Li SL (2015) Cell-surface vimentin: a mislocalized protein for isolating csVimentin(+) CD133(-) novel stem-like hepatocellular carcinoma cells expressing EMT markers. Int J Cancer 137(2):491–496
Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68(18):3033–3046
Weidle UH, Maisel D, Klostermann S, Schiller C, Weiss EH (2011) Intracellular proteins displayed on the surface of tumor cells as targets for therapeutic intervention with antibody-related agents. Cancer Genomics Proteomics 8(2):49–63
Li H, Meng QH, Noh H, Somaiah N, Torres KE, Xia X, Batth IS, Joseph CP, Liu M, Wang R, Li S (2018) Cell-surface vimentin-positive macrophage-like circulating tumor cells as a novel biomarker of metastatic gastrointestinal stromal tumors. Oncoimmunology 7(5):e1420450. https://doi.org/10.1080/2162402X.2017.1420450. eCollection 2018
Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM (2003) Vimentin is secreted by activated macrophages. Nat Cell Biol 5:59–63
Pall T, Pink A, Kasak L, Turkina M, Anderson W, Valkna A, Kogerman P (2011) Soluble CD44 interacts with intermediate filament protein vimentin on endothelial cell surface. PLoS One 6:e29305
Satelli A, Hu J, Xia X, Li S (2016) Potential function of exogenous vimentin on the activation of Wnt signaling pathway in cancer cells. J Cancer 7:1824–1832
Liu TA, Jan YJ, Ko BS, Liang SM, Chen SC, Wang J, Hsu C, Wu YM, Liou J-Y (2013) 14-3-3ε overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma. PLoS One 8:e57968
Sutoh-Yoneyama M, Hatakeyama S, Habuchi T, Inoue T, Nakamura T, Funyu T, Wiche G, Oyama C, Tsuboi S (2014) Vimentin intermediate filament and plectin provide a scaffold for invadopodia, faciliating cancer cell invasion and extravasation for metastasis. Eur J Cell Biol 93:157–169
Zhang MH, Lee JS, Kim HJ, Jin DI, Kim JI, Lee KJ, Seo JS (2006) HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis. Mol Cell Biochem 281:111–121
Wang RC, Wei Y, An Z, Zou Z, Xiao G, Bhagat G, White M, Reichelt J, Levine B (2012) Akt-mediated regulation of autophagy and tumorigenesis through beclin 1 phosphorylation. Science 338:956–959
Rogel MR, Soni PN, Troken JR, Sitikov A, Trejo HE, Ridge KM (2011) Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells. FASEB J 25:3873–3883
Glaser-Gaby L, Raiter A, Battler A, Hardy B (2011) Endothelial cell surface vimentin binding peptide induces angiogenesis under hypoxic/ischemic conditions. Microvasc Res 82:221–226
Thiagarajan PS, Yakubenko VP, Elsori DH, Yadav SP, Willard B, Tan CD, Rodoriguez ER, Febbraio M, Cathcart MK (2013) Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1. Cardiovasc Res 99:494–504
Henderson P, Wilson DC, Satsangi J, Stevens C (2012) A role for vimentin in chrohns disease. Autophagy 8:1695–1696
Ambrose J, Livitz M, Wessels D, Kuhl S, Lusche DF, Scherer A, Voss E, Soll DR (2015) Mediated coalescence: a possible mechanism for tumor cellular heterogeneity. Am J Cancer Res 5:3485–3504
Brentvill VA, Metheringham RL, Gunn B, Symonds P, Daniels I, Gijon M, Cook K, Xue W, Durrant LG (2016) Citrullinated vimentin presented on MHC-II in tumor cells is a target for CD4+ T-cell-mediated antitumor immunity. Cancer Res 76:548–560
Bay-Jensen AC, Karsdal MA, Vassiliadis E, Wichuk S, Marcher-Mikkelsen K, Lories R, Christiansen C, Maksymowych WP (2013) Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression. Arthritis Rheum 65:972–980
Planey SL, Keay SK, Zhang CO, Zacharias DA (2009) Palimitoylation of cytoskeleton associated protein 4 by DHHC2 regulates antiproliferative factor-mediated signaling. Am Soci Cell Biol 20:1456–1463
Yasui Y, Goto H, Matsui S, Manser E, Lim L, Nagata K, Inagaki M (2001) Protein kinase required for segregation of vimentin filaments in mitotic process. Oncogene 20:2868–2876
Wang L, Zhang J, Banerjee S, Barnes L, Sajja V, Liu Y, Guo B, Du Y, Agarmal MK, Wald DN, Wang Q, Yang J (2010) Sumoylation of vimentin354 is associated with PIAS3 inhibition of glioma cell migration. Oncotarget 1:620–627
Hugwil AV (2015) Antigenicity of the tumor-associated antigen vimentin epitope on ectosomes of brain tumor cell. Int J Cancer Res Dev 1:7–13
Da Q, Behymer M, Correa JI, Vijayan V, Cruz MA (2014) Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress. Blood 123:2715–2721
Glassy MC, Koda K (2002) The nature of an ideal therapeutic human antibody. Expert Opin Biol Ther 2:1–2
Lowery J, Guo M, Weitz DA, Kuezmarski E, Goldman RD (2016) Methods for determining the cellular function of vimentin intermidiate filaments. Methods Enzymol 568:391–421
Lam FW, Da Q, Guillory B, Cruz MA (2018) Recombinant human vimentin binds to P-selectin and blocks neutrophil capture and rolling on platelets and entothelium. J Immunol 200:1718–1726
Mukerjee S, McKnight M, Glassy M (1998) Immnoscreening protocols for the identification of clinically useful antibodies and antigens. Expert Opin Investig Drugs 7:373–389
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Babic, I., Kesari, S., Glassy, M.C. (2019). A Binding Potency Assay for Pritumumab and Ecto-Domain Vimentin. In: Steinitz, M. (eds) Human Monoclonal Antibodies. Methods in Molecular Biology, vol 1904. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8958-4_19
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8958-4_19
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8957-7
Online ISBN: 978-1-4939-8958-4
eBook Packages: Springer Protocols