Abstract: The present invention relates to an improved method for the production of antibodies to tumor-associated gangliosides using ganglioside lactones. The resulting antibodies are useful in the detection and treatment of tumors containing gangliosides. The present invention also relates to methods of treatment of tumors by active immunization using ganglioside lactones.
Abstract: An onco-developmentally regulated .alpha.-N-acetylgalactosaminyltransferase isolated as a component of a particulate membrane fraction separated from cell and tissue homogenates and having the following characteristics:(a) Activity in Various Cells and Tissues--present in human fetal lung fibroblasts, hepatoma tissues and placenta, but absent from normal adult liver, lung, kidney and spleen tissues;(b) Substrate Specificity--acts on polypeptides comprising a sequence val-thr-his-pro-gly-tyr by catalyzing u-N-acetylgalactosaminylation at the thr residue of the sequence;(c) Requirements for Metal Ion--requires metal ion for activity in 25 mM tris buffer, pH 7.6;(d) Optimal pH--optimal pH is about 7.6 assayed in hepatoma cell homogenate in tris buffer and at a pH of about 6 to about 7 assayed in hepatoma cell homogenate enzyme activity is higher in 2(N-morpholino)ethanesulfonic acid than in cacodylate buffer; and(e) Km--apparent Km for UDP - GalNAc is about 48 .mu.M.
Type:
Grant
Filed:
October 2, 1992
Date of Patent:
April 5, 1994
Assignees:
Fred Hutchinson Cancer Research Institute, The Biomembrane Institute, The Board of Regents of the University of Washington
Abstract: A method for preparing de-N-acylated forms of an N-acyl sugar-containing glycosphingolipid and lyso forms of glycosphingolipid comprising hydrolyzing the glycosphingolipids under mild alkaline conditions such that the N-acyl group of the sugar moiety is preferentially hydrolyzed. Substantially pure gangliosides containing de-N-acetyl-sialic acid isolated from natural sources. A culture medium for stimulating growth of human and animal cells comprising: essential nutrients for cell growth, and a cell growth stimulatory amount of one or more gangliosides containing de-N-acetyl-sialic acid. A method for stimulating growth of human and animal cells cultured in vitro with a cell growth stimulatory amount of one or more gangliosides containing de-N-acetyl-sialic acid.
Type:
Grant
Filed:
January 19, 1990
Date of Patent:
December 21, 1993
Assignee:
The Biomembrane Institute
Inventors:
Sen-itiroh Hakomori, Gustavo A. Nores, Nobuo Hanai, Taeko Dohi, Steven B. Levery, Mary Ellen K. Salyan, Hisao Nojiri
Abstract: O-glycosylation and O-glycosylation extension inhibitors influence selectin-dependent interactions between cells and between cells and platelets.
Abstract: A method of inhibiting tumor cell chemotactic and/or chemoinvasion motility comprising contacting the tumor cell with an inhibitory amount of an agent selected from the group consisting of sphingosine-1-phosphate, derivatives of sphingosine-1-phosphate and mimetics of the sphingosine-1-phosphate or of the derivatives. A method of inhibiting phagokinetic activity of tumor cells and neutrophils comprising contacting the cells with a phagokinetic inhibitory amount of an agent selected from the group consisting of sphingosine-1-phosphate, derivatives of sphingosine-1-phosphate, and mimetics of the sphingosine-1-phosphate or of the derivatives. A method of inhibiting tumor cell metastasis comprising administering to a host in need of treatment a metastasis inhibitory amount of an agent selected from the group consisting of sphingosine-1-phosphate, derivatives of sphingosine-1-phosphate, and mimetics of the sphingosine-1-phosphate or of the derivatives, and pharmaceutically acceptable salts of the agent.
Abstract: The invention relates to a novel compound, compositions and medicaments thereof and a method of inhibiting cell proliferation, platelet aggregation (induced by various factors), and inhibiting malignant phenotypes of tumor cells such as those having a metastatic property, using said compound, composition or medicament. N,N,N-trimethylsphingosine shows superior cell proliferation inhibitory and anti-metastatic activity over related compounds.
Type:
Grant
Filed:
May 7, 1992
Date of Patent:
September 28, 1993
Assignee:
The Biomembrane Institute
Inventors:
Yasuyuki Igarashi, Mahammad N. Ahmad, Hirofumi Okoshi, Sen-Itiroh Hakomori
Abstract: 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.
Type:
Grant
Filed:
November 6, 1991
Date of Patent:
August 31, 1993
Assignee:
The Biomembrane Institute
Inventors:
Edward Nudelman, Anil Singhal, Henrik Clausen, Sen-itiroh Hakomori
Abstract: The present invention relates to compositions which mediate antibody and ligand targeting of differentiation-inducers to tumor cells and methods for employing the same.
Abstract: 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.
Type:
Grant
Filed:
December 16, 1991
Date of Patent:
July 20, 1993
Assignee:
The Biomembrane Institute
Inventors:
Thomas J. Kjeldsen, Henrik Clausen, Anil Singhal, Tatsushi Toyokuni, Helio Takahashi, Sen-itiroh Hakomori
Abstract: Monoclonal antibody NUH2 produced by a hybridoma having ATCC deposit no. HB 9762. An isolated antigen capable of specifically binding to anti-human sperm antibodies including NUH2 and comprising at least an epitope having a sialyl I structure, and any analogues derived from said antigen. Methods of using the monoclonal antibody and antigen for contraception and treating infertility in human females.
Type:
Grant
Filed:
July 15, 1988
Date of Patent:
July 13, 1993
Assignees:
The Biomembrane Institute, Hyogo Medical College
Inventors:
Edward Nudelman, Tokio Kaizu, Ulla Mandel-Clausen, Steven B. Levery, Sen-itiroh Hakomori, Yoshiyuki Tsuji, Shinzo Isojima
Abstract: The present invention discloses trifluorofucoses and methods of making the same. Also disclosed are trifluorofucose analogs of fucose-containing oligosaccharides, and conjugates of trifluorofucose. Compositions are prepared which combine the trifluorofucose-containing oligosaccharides or trifluorofucose conjugates of the present invention with a pharmaceutically acceptable carrier or diluent. Tumor cell metastasis, autoimmune responses or inhibition of an inflammatory process may be inhibited by such compositions.
Abstract: The invention relates to a novel compound, compositions and medicaments thereof and a method of inhibiting cell proliferation, platelet aggregation (induced by various factors) and inhibiting malignant phenotypes of tumor cells such as those having a metastatic property, and modulating cell adhesion molecule expression and function using said compound, composition or medicament. N,N,N-trimethylsphingosine shows superior cell proliferation inhibitory an anti-metastatic activity over related compounds.
Type:
Grant
Filed:
July 2, 1991
Date of Patent:
September 29, 1992
Assignee:
Biomembrane Institute
Inventors:
Kazuko Handa, Yasuyuki Igarashi, Mahammad N. Ahmad, Sen-Itiroh Hakomori
Abstract: The invention relates to a novel compound, compositions and medicaments thereof and a method of inhibiting cell proliferation, platelet aggregation (induced by various factors), and inhibiting malignant phenotypes of tumor cells such as those having a metastatic property, using said compound, composition or medicament. N,N,N-trimethylsphingosine shows superior cell proliferation inhibitory and anti-metastatic activity over related compounds.
Type:
Grant
Filed:
December 31, 1990
Date of Patent:
August 11, 1992
Assignee:
Biomembrane Institute
Inventors:
Yasuyuki Igarashi, Mahammad N. Ahmad, Hirofumi Okoshi, Sen-Itiroh Hakomori
Abstract: 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.
Type:
Grant
Filed:
August 31, 1989
Date of Patent:
November 26, 1991
Assignee:
The Biomembrane Institute
Inventors:
Henrik Clausen, Fumi-ichiro Yamamoto, Thayer White, Sen-itiroh Hakomori
Abstract: A substantially pure unbranched ceramide polysaccharide type 2 chain compound having the following structure: ##STR1## wherein Gal represents galactose, GlcNAc represents N-acetylglucosamine, Fuc represents fucose Glc represents glucose and Cer represents ceramide. A substantially pure unbranched ceramide polysaccharide type 2 chain compound having the following structure: ##STR2## wherein Gal represents galatose, GlcNAc represents N-acetylglucosamine. Fuc represents fucose, Glc represents glucose, Cer represents ceramide and NeuAc represents sialic acid. Antibodies that are specific to portions of the above-described compounds, wherein the portions comprise the internal .alpha.1-.fwdarw.3 fucosyl residue and/or the terminal sialic acid residue. Immuogens for producing antibodies to the above-described compounds or portions thereof. A method of actively immunizing against tumors that express the above-described compounds.
Type:
Grant
Filed:
May 31, 1988
Date of Patent:
July 9, 1991
Assignee:
The Biomembrane Institute
Inventors:
Edward D. Nudelman, Steven B. Levery, Mark R. Stroud, Mary Ellen K. Salvan, Sen-itiroh Hakomori
Abstract: 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.
Abstract: 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.