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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4494-4502. Prepublished online as a Blood First Edition Paper on August 10, 2009; DOI 10.1182/blood-2009-05-222786. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-05-222786v1 114/20/4494    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Baskar, S. Articles by Rader, C. PubMed PubMed Citation Articles by Baskar, S. Articles by Rader, C. Related Collections Transplantation Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA 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 Sivasubramanian Baskar1, Jessica M. Suschak1, Ivan Samija1, Ramaprasad Srinivasan2, Richard W. Childs2, Steven Z. Pavletic1, Michael R. Bishop1, and Christoph Rader1 1 Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, and 2 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 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 [ClinicalTrials.gov] and NCT00003838 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hunting for the Achilles' heel of CLL John C. Byrd Blood 2009 114: 4324. [Full Text] [PDF] This article has been cited by other articles: J. C. Byrd Hunting for the Achilles' heel of CLL Blood, November 12, 2009; 114(20): 4324 - 4324. [Full Text] [PDF]

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