title: Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activity.
abstract: CD1A is a cell surface protein expressed on Langerhans cells and cortical thymocytes that could potentially be used as an immunotherapeutic target in Langerhans Cell Histiocytosis (LCH), the cortical subtype of T-cell acute lymphocytic leukaemia (T-ALL) and other CD1A-positive tumours. The monoclonal antibody (mAb) CR2113 was selected from a panel of six fully human mAbs isolated from a semi-synthetic phage display library, based on specificity and avidity against cells expressing CD1 antigen variants. CR2113 recognized CD1A in T-ALL cell lines and patient samples. Confocal microscopy revealed that the CR2113-CD1A complex was internalized at 37°C. Furthermore, while CR2113 induced moderate complement-dependent cytotoxicity (CDC), potent antibody-dependent cell cytotoxicity (ADCC) activity was observed against CD1A expressing cell lines as well as T-ALL cell lines and T-ALL patient samples. In vivo experiments showed that CR2113 as a naked antibody has modest but specific anti-tumour activity against CD1A-expressing tumours. CR2113 is a high-affinity human anti-CD1A mAb with significant ADCC activity. These properties make CR2113 a candidate for clinical diagnostic imaging and therapeutic targeting of LCH as well as potential use in other clinical applications.
authors.affiliation: Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Gitanjali I
authors.initials: GI
authors.lastname: Bechan
authors.forename: David W
authors.initials: DW
authors.lastname: Lee
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Zajonc
authors.forename: Diana
authors.initials: D
authors.lastname: Heckel
authors.forename: Rena
authors.initials: R
authors.lastname: Xian
authors.forename: Mark
authors.initials: M
authors.lastname: Throsby
authors.forename: Marja
authors.initials: M
authors.lastname: van Meijer
authors.forename: Wilfred T V
authors.initials: WT
authors.lastname: Germeraad
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kruisbeek
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000302:isolation & purification; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019151:Peptide Library; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018949:Antigens, CD1; C419393:CD1a antigen; D007074:Immunoglobulin G; D019151:Peptide Library; D057127:Single-Chain Antibodies