The Biomembrane Institute

Jichi Medical School

Henrik Clausen

Sen-Itiroh Hakomori

Anil Singhal

Edward D Nudelman

Tatsushi Toyokuni

Thomas J Kjeldsen

Helio K Takahashi

Sen-itiroh Hakomori

Mark R Stroud

Fumi-ichiro Yamamoto

Thayer White

Hisao Nojiri

Khalid K Sadozai

Kazuo Muroi

Toshio Suda

A method of producing monoclonal antibodies that bind to human cancer-associated mucin-type glycoprotein antigens comprising: (1) immunizing a host with a core structure of a mucin-type glycoprotein; (2) fusing splenocytes from said immunized host with myeloma cells to form hybridoma cells; (3) culturing said hybridoma cells on selective medium; (4) selecting hybridoma cells surviving step (3) that secrete antibody that binds to said core structure of a mucin-type glycoprotein; (5) cloning said selected hybridoma cells from step (4); (6) culturing said cloned hybridoma cells; and (7) recovering said antibody. Hybridomas and monoclonal antibodies produced by the above-described method. Methods of passive and active immunization employing the monoclonal antibodies and mucin-type glycoproteins or synthetic oligosaccharide-carrier conjugates.

Monoclonal antibodies and vaccine development directed to human

A vaccine and method to prevent growth and replication of cancer cells that express a core structure of a mucin-type glycoprotein is disclosed. The vaccine comprises: (a) a pharmaceutically effective amount of an antigen comprising a purified mucin-type glycoprotein or a chemically synthesized mucin-type glycoprotein carbohydrate determinant conjugated to a carrier peptide or macromolecule, wherein said mucin-type glycoprotein expresses or carries the core structure of a mucin-type glycoprotein expressed on said cancer cells; and (b) a pharmaceutically acceptable carrier including natural or synthetic adjuvants. The method comprises administering the above-described vaccine to a host. A medicament and method for treating cancer wherein the cancer cells express a core structure of a mucin-type glycoprotein is disclosed. The medicament comprises: (a) a pharmaceutically effective amount of an anti-cancer antibody or fragment comprising a binding site thereof, said anti-cancer antibody having been produced against a purified core structure of a mucin-type glycoprotein; and (b) a pharmaceutically acceptable carrier, diluent or excipient. The method comprises administering the above-described medicament to a host.

A process for preparing difucosyl Y.sub.2 antigen (dimeric Le.sup.x) , said process comprising: (1) preparing a lactonorhexaosylceramide backbone or a lactonorhexaosylsaccharide backbone linked to a carrier molecule; and (2) enzymatically fucosylating said backbone at the III.sup.3 and V.sup.3 positions through an .alpha.1.fwdarw.3 linkage. A process for preparing Le.sup.y antigen analogues, said process comprising: (1) preparing a lactonorhexaosyl-ceramide backbone or a lactonorhexaosylsaccharide backbone linked to a carrier molecule; and (2) enzymatically fucosylating said backbone at the terminal .beta.-Gal through an .alpha.1.fwdarw.2 linkage; and (3) enzymatically fucosylating said backbone at one or more positions through an .alpha.1.fwdarw.3 linkage, provided that steps (2) and (3) can be conducted simultaneously or in any order. A process for preparing a fucosylated lactonorhexaosylceramide, lactonorhexaosylsaccharide linked to a carrier molecule or higher analogues thereof, said process comprising: (1) preparing a lactonorhexaosylceramide backbone, a lactonorhexaosylsaccharide backbone linked to a carrier molecule or backbones of higher analogues thereof; and (2) enzymatically fucosylating one or more residues of said backbone. A process for preparing sialyl Le.sup.x and sialyl dimeric Le.sup.x.

Synthesis of Le.sup.x ; dimeric Le.sup.x (difucosyl Y.sub.2 ; III.sup.3

A method of producing monoclonal antibodies that bind to tumor-associated gangliosides, the method comprising: (1) immunizing a host with tumor cells; (2) boosting the host with a suspension comprising a mixture of tumor cell membrane and at least one purified lactonized tumor-associated ganglioside; (3) boosting the host with an immunogen comprising a lactone of a tumor associated ganglioside adsorbed on or incorporated into a carrier; (4) fusing immunized cells from the host with myeloma cells to form hybridoma cells; (5) selecting hybridoma cells that produce antibody that binds to the ganglioside of step (3); (6) culturing the selected hybridoma cells; and (7) recovering the antibody.

Blood treatment method

A method of producing monoclonal antibodies that bind to tumor-associated gangliosides, the method comprising: (1) immunizing a host with tumor cells; (2) boosting the host with a suspension comprising a mixture of tumor cell membrane and at least one purified lactonized tumor-associated ganglioside; (3) boosting the host with an immunogen comprising a lactone of a tumor associated ganglioside adsorbed on or incorporated into a carrier; (4) fusing immunized cells from the host with myeloma cells to form hybridoma cells: (5) selecting hybridoma cells that produce antibody that binds to the ganglioside of step (3); (6) culturing the selected hybridoma cells; and (7) recovering the antibody. Hybridomas and monoclonal antibodies produced by the above-described method. A passive immunization method for treatment of tumors containing gangliosides comprising administering to a subject: (A) a pharmaceutically effective amount of an antibody produced by the above described method. A method for detecting tumors containing gangliosides comprising: (A) contacting a test sample with an antibody produced by the above described method; and (B) assaying for the specific binding of the antibody to antigen in the test sample.

Method for the production of monoclonal antibodies directed to

A method of producing monoclonal antibodies that bind to human cancer-associated mucin-type glycoprotein antigens comprising: (1) immunizing a host with a core structure of a mucin-type glycoprotein: (2) fusing splenocytes from said immunized host with myeloma cells to form hybridoma cells; (3) culturing said hybridoma cells on selective medium; (4) selecting hybridoma cells surviving step (3) that secrete antibody that binds to said core structure of a mucin-type glycoprotein; (5) cloning said selected hybridoma cells from step (4); (6) culturing said cloned hybridoma cells; and (7) recovering said antibody. Hybridomas and monoclonal antibodies produced by the above-described method. Methods of passive and active immunization employing the monoclonal antibodies and mucin-type glycoproteins or synthetic oligosaccharide-carrier conjugates.

The genes defining the ABO histo-blood groups are disclosed. Methods for identification of histo-blood group ABO status are provided. The methods include the use of DNA probes or size separation of DNA fragments unique to a blood group status. The present invention also discloses DNA constructs, recombinant methods for providing histo-blood glycosyltransferases, methods for tumor suppression, purified histo-blood group glycosyltransferases, and antibodies produced therefrom which bind to protein epitopes.

Purified histo-blood group A glycosyltransferase and antibodies thereto

The present invention relates to antigens present in blood group A and blood group AB erythrocytes but absent in blood group B and blood group O erythrocytes. More specifically, the present invention relates to A-associated H-antigens having the following structure: ##STR1## wherein X is a sugar residue and n=O or a positive integer and wherein R is a primary amino group containing material selected from the group consisting of a polypeptide, a primary amino group containing lipid and a primary amino group containing support; monoclonal antibodies specific thereto and methods for employing the same in blood typing.

A-associated H-antigens, monoclonal antibodies specific thereto and

The present invention relates to antigens present in blood group A and blood group AB erythrocytes but absent in blood group B and blood group O erythrocytes. More specifically, the present invention relates to A-associated H-antigens having the following structure: ##STR1## wherein X is a sugar residue and n=0 or a positive integer and wherein R is a primary amino group containing material selected from the group consisting of a polypeptide, a primary amino group containing liquid and a primary amino group containing support; monoclonal antibodies specific thereto and methods for employing the same in blood typing.

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Seattle, WA, United States of America

Henrik Clausen