Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin
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Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin. / Müthing, Johannes; Meisen, Iris; Kniep, Bernhard; Haier, Jörg; Senninger, Norbert; Neumann, Ulrich; Langer, Martin; Witthohn, Klaus; Milosević, Jadranka; Peter-Katalinić, Jasna.
In: FASEB J, Vol. 19, No. 1, 01.2005, p. 103-5.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin
AU - Müthing, Johannes
AU - Meisen, Iris
AU - Kniep, Bernhard
AU - Haier, Jörg
AU - Senninger, Norbert
AU - Neumann, Ulrich
AU - Langer, Martin
AU - Witthohn, Klaus
AU - Milosević, Jadranka
AU - Peter-Katalinić, Jasna
PY - 2005/1
Y1 - 2005/1
N2 - The anticancer drug rViscumin, currently under clinical development, has been shown in previous studies to be a sialic acid specific ribosome inactivating protein (RIP). Comparative binding assays with the CD75s-specific monoclonal antibodies HB6 and J3-89 revealed rViscumin to be a CD75s-specific RIP due to identical binding characteristics toward CD75s gangliosides. The receptor gangliosides are IV6nLc4Cer, VI6nLc6Cer, and the newly characterized ganglioside VIII6nLc8Cer, all three carrying the Neu5Acalpha2-6Galbeta1-4GlcNAc motif. To elucidate the clinical potential of the rViscumin targets, CD75s gangliosides were determined in several randomly collected gastrointestinal tumors. The majority of the tumors showed an enhanced expression of CD75s gangliosides compared with the unaffected tissues. The rViscumin binding specificity was further investigated with reference glycoproteins carrying sialylated and desialylated type II N-glycans. Comparative Western blots of rViscumin and ricin, an rViscumin homologous but galactoside-specific RIP, revealed specific recognition of type II N-glycans with CD75s determinants by rViscumin, whereas ricin failed to react with terminally sialylated oligosaccharides such as CD75s motifs and others. This strict binding specificity of rViscumin and the increased expression of CD75s gangliosides in various tumors suggest this anticancer drug as a promising candidate for an individualised adjuvant therapy of human tumors.
AB - The anticancer drug rViscumin, currently under clinical development, has been shown in previous studies to be a sialic acid specific ribosome inactivating protein (RIP). Comparative binding assays with the CD75s-specific monoclonal antibodies HB6 and J3-89 revealed rViscumin to be a CD75s-specific RIP due to identical binding characteristics toward CD75s gangliosides. The receptor gangliosides are IV6nLc4Cer, VI6nLc6Cer, and the newly characterized ganglioside VIII6nLc8Cer, all three carrying the Neu5Acalpha2-6Galbeta1-4GlcNAc motif. To elucidate the clinical potential of the rViscumin targets, CD75s gangliosides were determined in several randomly collected gastrointestinal tumors. The majority of the tumors showed an enhanced expression of CD75s gangliosides compared with the unaffected tissues. The rViscumin binding specificity was further investigated with reference glycoproteins carrying sialylated and desialylated type II N-glycans. Comparative Western blots of rViscumin and ricin, an rViscumin homologous but galactoside-specific RIP, revealed specific recognition of type II N-glycans with CD75s determinants by rViscumin, whereas ricin failed to react with terminally sialylated oligosaccharides such as CD75s motifs and others. This strict binding specificity of rViscumin and the increased expression of CD75s gangliosides in various tumors suggest this anticancer drug as a promising candidate for an individualised adjuvant therapy of human tumors.
KW - Antibodies, Monoclonal
KW - Antigens, CD
KW - Antigens, Tumor-Associated, Carbohydrate
KW - Antineoplastic Agents
KW - Blotting, Western
KW - Brain
KW - Chromatography, Thin Layer
KW - Electrophoresis, Polyacrylamide Gel
KW - G(M1) Ganglioside
KW - Gangliosides
KW - Gastrointestinal Neoplasms
KW - Glycoproteins
KW - Granulocytes
KW - Humans
KW - Models, Statistical
KW - Plant Preparations
KW - Plant Proteins
KW - Receptors, Drug
KW - Ribosome Inactivating Proteins, Type 2
KW - Ricin
KW - Sialyltransferases
KW - Spectrometry, Mass, Electrospray Ionization
KW - Toxins, Biological
U2 - 10.1096/fj.04-2494fje
DO - 10.1096/fj.04-2494fje
M3 - SCORING: Journal article
C2 - 15520251
VL - 19
SP - 103
EP - 105
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 1
ER -