Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Baskar, S.
  • Suschak, J. M.
  • Samija, I.
  • Srinivasan, R.
  • Childs, R. W.
  • Pavletic, S. Z.
  • Bishop, M. R.
  • Rader, Christoph

publication date

  • November 2009

journal

  • Blood  Journal

abstract

  • Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

subject areas

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Clinical Trials as Topic
  • Data Mining
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunoglobulin Fab Fragments
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Peptide Library
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Homologous
scroll to property group menus

Identity

PubMed Central ID

  • PMC2777128

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-05-222786

PubMed ID

  • 19667400
scroll to property group menus

Additional Document Info

start page

  • 4494

end page

  • 4502

volume

  • 114

issue

  • 20

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support