Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activity

Gitanjali I. Bechan, David W. Lee, Dirk M. Zajonc, Diana Heckel, Rena Xian, Mark Throsby, Marja van Meijer, Wilfred T.V. Germeraad, Anna M. Kruisbeek, R. Maarten Egeler, Robert J. Arceci

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalBritish journal of haematology
Volume159
Issue number3
DOIs
StatePublished - Nov 1 2012

Keywords

  • CD1A
  • Immunotherapy
  • Langerhans cell histiocytosis
  • Monoclonal antibody
  • T-lineage acute lymphoblastic leukaemia

ASJC Scopus subject areas

  • Hematology

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    Bechan, G. I., Lee, D. W., Zajonc, D. M., Heckel, D., Xian, R., Throsby, M., van Meijer, M., Germeraad, W. T. V., Kruisbeek, A. M., Egeler, R. M., & Arceci, R. J. (2012). Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activity. British journal of haematology, 159(3), 299-310. https://doi.org/10.1111/bjh.12033