Antibodies Selected from Combinatorial Libraries Block a Tumor Antigen That Plays a Key Role in Immunomodulation

We searched for cell-surface-associated proteins overexpressed on B cell chronic lymphocytic leukemia (CLL) to use as therapeutic antibody targets. Antibodies binding the immunosuppressive molecule CD200 were identified by cell panning of an antibody phage display library derived from rabbits immuni...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-01, Vol.103 (4), p.1041-1046
Main Authors: McWhirter, John R., Kretz-Rommel, Anke, Saven, Alan, Maruyama, Toshiaki, Potter, Kathleen N., Mockridge, C. Ian, Ravey, E. Prenn, Qin, Fenghua, Bowdish, Katherine S.
Format: Article
Language:English
Subjects:
Antibodies
Antibodies - chemistry
Antibodies, Monoclonal - chemistry
Antigens
Antigens, Neoplasm
B lymphocytes
B-Lymphocytes - metabolism
Bacteriophages
Biological Sciences
Cell Line
Cell Line, Tumor
Cell lines
Cell Membrane - metabolism
Cell Separation
Chronic lymphocytic leukemia
Cytokines
Cytokines - metabolism
Dendritic cells
Dendritic Cells - cytology
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunoglobulin Fragments - chemistry
Immunoglobulins
Immunology
Immunoprecipitation
Immunosuppressive Agents - pharmacology
Immunotherapy - methods
Interleukin-2 - metabolism
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukocytes, Mononuclear - metabolism
Libraries
Lymphocyte Culture Test, Mixed
Lymphocytes - immunology
Macrophages - metabolism
Mass Spectrometry
Monocytes - metabolism
Peptide Library
Proteins
T lymphocytes
T-Lymphocytes, Regulatory - cytology
Th1 Cells
Th2 Cells - immunology
Tumors
Up regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We searched for cell-surface-associated proteins overexpressed on B cell chronic lymphocytic leukemia (CLL) to use as therapeutic antibody targets. Antibodies binding the immunosuppressive molecule CD200 were identified by cell panning of an antibody phage display library derived from rabbits immunized with primary CLL cells. B cells from 87 CLL patients exhibited 1.6- to 5.4-fold cellsurface up-regulation of CD200 relative to normal B cells. An effect of increased CD200 expression by CLL cells on the immune system was evaluated in mixed lymphocyte reactions. Addition of primary CLL but not normal B cells to macrophages and T cells down-regulated the Th1 response, as seen by a 50-95% reduction in secreted IL-2 and IFN-γ. Antibodies to CD200 prevented downregulation of the Th1 response in most B cell CLL samples evaluated, indicating abrogation of the CD200/CD200R interaction can be sufficient to restore the Th1 response. A disease-progression-associated shift of the immune response from Th1 to Th2 has been observed in numerous cancers. Because this cytokine shift is also believed to promote the induction of regulatory T cells, reverting the immune response to Th1 through direct targeting of the cancer cells may provide therapeutic benefits in CLL by encouraging a cytotoxic T cell response.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0510081103