PubMed:36977722 JSONTXT

{"project":"GlyCosmos15-Species","denotations":[{"id":"17991","span":{"begin":153,"end":158},"obj":"Species"},{"id":"17996","span":{"begin":970,"end":975},"obj":"Species"},{"id":"18005","span":{"begin":295,"end":300},"obj":"Species"}],"attributes":[{"id":"A17991","pred":"db_id","subj":"17991","obj":"9606"},{"id":"A17996","pred":"db_id","subj":"17996","obj":"10090"},{"id":"A18005","pred":"db_id","subj":"18005","obj":"9606"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":106,"end":116},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G57321FI"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G57321FI"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":22,"end":28},"obj":"Disease"},{"id":"T2","span":{"begin":159,"end":169},"obj":"Disease"},{"id":"T3","span":{"begin":866,"end":879},"obj":"Disease"},{"id":"T4","span":{"begin":930,"end":935},"obj":"Disease"},{"id":"T5","span":{"begin":1052,"end":1057},"obj":"Disease"},{"id":"T6","span":{"begin":1079,"end":1085},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0004993"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":106,"end":116},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0021"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":159,"end":169},"obj":"Phenotype"},{"id":"T2","span":{"begin":866,"end":879},"obj":"Phenotype"},{"id":"T3","span":{"begin":930,"end":935},"obj":"Phenotype"},{"id":"T4","span":{"begin":1052,"end":1057},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0030731"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0003002"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002664"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-NCBITAXON","denotations":[{"id":"T1","span":{"begin":153,"end":158},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":295,"end":300},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":970,"end":975},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"10088"},{"id":"A4","pred":"db_id","subj":"T3","obj":"10090"}],"namespaces":[{"prefix":"_base","uri":"https://glycosmos.org/organisms/"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":873,"end":884},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0001064"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":734,"end":749},"obj":"Body_part"},{"id":"T2","span":{"begin":866,"end":872},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005576"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":106,"end":116},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0021"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":74},"obj":"Sentence"},{"id":"T2","span":{"begin":75,"end":234},"obj":"Sentence"},{"id":"T3","span":{"begin":235,"end":342},"obj":"Sentence"},{"id":"T4","span":{"begin":343,"end":477},"obj":"Sentence"},{"id":"T5","span":{"begin":478,"end":603},"obj":"Sentence"},{"id":"T6","span":{"begin":604,"end":803},"obj":"Sentence"},{"id":"T7","span":{"begin":804,"end":982},"obj":"Sentence"},{"id":"T8","span":{"begin":983,"end":1086},"obj":"Sentence"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":106,"end":116},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G57321FI"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G57321FI"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":159,"end":169},"obj":"Disease"},{"id":"T2","span":{"begin":866,"end":879},"obj":"Disease"},{"id":"T4","span":{"begin":930,"end":935},"obj":"Disease"},{"id":"T5","span":{"begin":1052,"end":1057},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0004993"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"MONDO:0004989"},{"id":"A3","pred":"mondo_id","subj":"T2","obj":"MONDO:0007254"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"MONDO:0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"MONDO:0005070"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":866,"end":872},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:9601"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":153,"end":158},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":295,"end":300},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":970,"end":975},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"10088"},{"id":"A4","pred":"db_id","subj":"T3","obj":"10090"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":734,"end":749},"obj":"Body_part"},{"id":"T2","span":{"begin":866,"end":872},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005576"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":159,"end":169},"obj":"Phenotype"},{"id":"T2","span":{"begin":866,"end":879},"obj":"Phenotype"},{"id":"T3","span":{"begin":930,"end":935},"obj":"Phenotype"},{"id":"T4","span":{"begin":1052,"end":1057},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0030731"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0003002"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002664"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":873,"end":884},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0001064"}],"text":"Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.\nThe aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors."}