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METHOD FOR PRODUCING ANTIGEN-SPECIFIC B CELL POPULATION
Human Antibody Production In vitro by B Cell

Field
     Antibody drug, Antibody production

Keywords
     Antigen, B-cell, Antibody, Antibody drug, Antibody production

Advantages
     The humanized antibody, as a mainstream antibody drug, is currently produced by genetically
     modifying the antibodies derived from mice or other animals, a process that takes an enormous
     amount of time and effort. Since it is dependent on animal immunity, good antibodies cannot be
     obtained for the antigen with high homology among species because of the self-tolerance in
     individual animals. It is difficult to immunize antigens with high individual toxicity. This invention,
     based on the method where human B cells are cultured in vitro and antigen-specific B cells are
     selectively concentrated, can eliminate the problems mentioned above and can theoretically
     produce a perfect humanized antibody to any antigen. In cases where B cells derived from
     animals other than humans are used, the antibody gene can be isolated from the concentrated
     and isolated antigen-specific B cells to create antigen-specific monoclonal antibodies without
     immunizing animals or creating/screening hybridomas.
     In accordance with the present patent, it is now possible that an antibody which is highly toxic
     and is unable to be produced in animals and also an antibody which has far higher effect are
     taken out by a cell culturing method.  Since an antigen such as avian influenza is able to be used
     just as it is, an antibody having a very high effect is able to be taken out.

Abstract
We provide the following method to easily manufacture a population of antigen-specific B cells in order to produce antibodies specific to a particular antigen in vitro. This is a method to select B cells specific to the above mentioned particular antigen and to obtain a population of antigen-specific B cells that include IgG-positive B cells specific to the above mentioned particular antigen by: adding IL-4 or IL-21 to B cells being stimulated through CD40 and BAFF receptor by CD40L and 40LB (fibroblast cell line where BAFF was developed) etc; or applying stimulation of the above mentioned particular antigen, FasL, CD40L, BAFF, and IL-21 to IgG-positive B cells which were cultured by consecutively adding IL-4 and IL-21 and then significantly grown.
 A technique where human B cells are promulgated in vitro to an extent of not less than 105 has been established.  On the basis of the culturing conditions at that time, an antigen has been proposed and a method for the selection of an antibody having higher affinity has been established.


         
Inventor
    Prof. Daisuke Kitamura et al. (Tokyo University of Science)


Patent Publication No
    (APPLICATION NUMBER, FILING DATE)
    WO2010068868 (Oct. 25, 2010)
    (PUBLICATION NUMBER, PUBLICATION DATE)
    WO2011052545 (May 5, 2011)


Internal file number
    LSP:62
    G2010-014 (T2009-045)



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