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A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity

  1. Author:
    Feng, Y.
    Xiao, X. D.
    Zhu, Z. Y.
    Streaker, E.
    Ho, M.
    Pastan, I.
    Dimitrov, D. S.

  2. Author Address

    Feng, Yang, Xiao, Xiaodong, Zhu, Zhongyu, Streaker, Emily, Dimitrov, Dimiter S.] NCI, Ctr Canc Res, Nanobiol Program, Prot Interact Grp,NIH, Frederick, MD 21702 USA. [Zhu, Zhongyu] NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Ho, Mitchell, Pastan, Ira] Natl Canc Inst Frederick, Mol Biol Lab, CCR, NIH, Bethesda, MD USA.
    1. Year: 2009
    2. Date: May
  2. Journal: Molecular Cancer Therapeutics
    1. 8
    2. 5
    3. Pages: 1113-1118
  4. Type of Article: Article
  5. ISSN: 1538-8514
  1. Abstract:

    Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers. However, all currently available antibodies against mesothelin are either murine or chimeric, which could limit their use because of increased likelihood of immunogenicity compared with fully human antibodies. Here, we report the identification and characterization of a novel fully human monoclonal antibody, m912, which was isolated from a human Fab library by panning against recombinant mesothelin. This antibody in scFv, Fab, and IgG1 formats bound specifically and with high affinity (equilibrium dissociation constant in the nmol/L range) to cell surf ace-associated human mesothelin and to recombinant mesothelin. It specifically lysed cancer cells engineered to express mesothelin in the presence of peripheral blood mononuclear cells isolated from healthy donors most likely by antibody-dependent cellular cytotoxicity. M912 is the first reported fully human monoclonal antibody to mesothelin, which has potential for cancer treatment and diagnosis. [Mol Cancer Ther 2009,8(5):1113-8]

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External Sources

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  2. DOI: 10.1158/1535-7163.mct-08-0945
  3. PMID: 19417159
  4. View record in Web of Science®
  5. WOS: 000266189900015

Library Notes

  1. Fiscal Year: FY2008-2009
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