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Tumor immunolocalization using 124 I-iodine-labeled JAA-F11 antibody to Thomsen-Friedenreich alpha-linked antigen.

ABSTRACT: Clinical immunolocalization has been attempted by others with an anti-Thomsen-Friedenreich antigen (TF-Ag) mAb that bound both alpha- and beta-linked TF-Ag. In this report, 124 I-labeled mAb JAA-F11 specific for alpha-linked TF-Ag showed higher tumor specificity in in vivo micro-positron emission tomography (micro-PET) of the mouse mammary adenocarcinoma line, 4T1, showing no preferential uptake by the kidney. Labeled product remained localized in the tumor for at least 20 days. Glycan array analysis showed structural specificity of the antibody.

SUBMITTER: Chaturvedi R

PROVIDER: S-EPMC3192430 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Tumor immunolocalization using 124 I-iodine-labeled JAA-F11 antibody to Thomsen-Friedenreich alpha-linked antigen.

Chaturvedi Richa R Heimburg Jamie J Yan Jun J Koury Stephen S Sajjad Munawwar M Abdel-Nabi Hani H HH Rittenhouse-Olson Kate K

Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 20070817 3

Clinical immunolocalization has been attempted by others with an anti-Thomsen-Friedenreich antigen (TF-Ag) mAb that bound both alpha- and beta-linked TF-Ag. In this report, 124 I-labeled mAb JAA-F11 specific for alpha-linked TF-Ag showed higher tumor specificity in in vivo micro-positron emission tomography (micro-PET) of the mouse mammary adenocarcinoma line, 4T1, showing no preferential uptake by the kidney. Labeled product remained localized in the tumor for at least 20 days. Glycan array ana ...[more]

PMID: 17890096

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Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.

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Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor.

Project description:Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins that mediate adaptive immunity in jawless vertebrates. VLRs were recently shown to recognize glycans, such as the tumor-associated Thomsen-Friedenreich antigen (TF?; Gal?1-3GalNAc?), with a selectivity rivaling or exceeding that of lectins and antibodies. To understand the basis for TF? recognition by one such VLR (VLRB.aGPA.23), we measured thermodynamic parameters for the binding interaction and determined the structure of the VLRB.aGPA.23-TF? complex to 2.2 ? resolution. In the structure, four tryptophan residues form a tight hydrophobic cage encasing the TF? disaccharide that completely excludes buried water molecules. This cage together with hydrogen bonding of sugar hydroxyls to polar side chains explains the exquisite selectivity of VLRB.aGPA.23. The topology of the glycan-binding site of VLRB.aGPA.23 differs markedly from those of lectins or antibodies, which typically consist of long, convex grooves for accommodating the oligosaccharide. Instead, the TF? disaccharide is sandwiched between a variable loop and the concave surface of the VLR formed by the ?-strands of the leucine-rich repeat modules. Longer oligosaccharides are predicted to extend perpendicularly across the ?-strands, requiring them to bend to match the concavity of the VLR solenoid.

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Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy.

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Structural basis for distinct binding properties of the human galectins to Thomsen-Friedenreich antigen.

Project description:The Thomsen-Friedenreich (TF or T) antigen, Gal?1-3GalNAc?1-O-Ser/Thr, is the core 1 structure of O-linked mucin type glycans appearing in tumor-associated glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a potential ligand for the human endogenous galectins. It has been reported that human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related functions via specifically recognizing TF antigen. However, the detailed binding properties have not been clarified and structurally characterized. In this work, first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed with TF antigen and derivatives, TFN and GM1, were then determined. These structures show a unique Glu-water-Arg-water motif-based mode as previously observed in the mushroom galectin AAL. The observation demonstrates that this recognition mode is commonly adopted by TF-binding galectins, either as endogenous or exogenous ones. The detailed structural comparisons between Gal-1 and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif ((51)AHGDA(55)) at the loop (g1-L4) connecting ?-strands 4 and 5 of Gal-1 produces a serious steric hindrance for TF binding. This motif is the main structural basis for Gal-1 with the low affinity to TF antigen. These findings provide the intrinsic structural elements for regulating the TF-binding activity of Gal-1 in some special conditions and also show certain target and approach for mediating some tumor-related bioactivities of human galectins.

| S-EPMC3176802 | biostudies-literature

Interaction of the Oncofetal Thomsen-Friedenreich Antigen with Galectins in Cancer Progression and Metastasis.

Project description:Aberrant glycosylation of cell membrane proteins is a universal feature of cancer cells. One of the most common glycosylation changes in epithelial cancer is the increased occurrence of the oncofetal Thomsen-Friedenreich disaccharide Galβ1-3GalNAc (T or TF antigen), which appears in about 90% of cancers but is rarely seen in normal epithelium. Over the past few years, increasing evidence has revealed that the increased appearance of TF antigen on cancer cell surface plays an active role in promoting cancer progression and metastasis by interaction with the β-galactoside-binding proteins, galectins, which themselves are also frequently overexpressed in cancer and pre-cancerous conditions. This review summarizes the current understanding of the molecular mechanism of the increased TF occurrence in cancer, the structural nature, and biological impact of TF interaction with galectins, in particular galectin-1 and -3, on cancer progression and metastasis.

| S-EPMC4814717 | biostudies-literature

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