Novel Anti-CD70 Antibody Drug Conjugate for the Treatment of Adult T-Cell Leukemia (ATL).

Background/aim: Adult T-cell leukemia (ATL) is a hematological malignancy caused by infection with human T-cell leukemia virus type 1 (HTLV-1). Chemotherapy, antibody therapy, and bone marrow transplantation are used to treat this disease, however, median survival time has not been significantly improved. Our aim was to develop and evaluate a novel antibody-drug conjugate (ADC) with regards to cell cytotoxicity and target specificity.

Synthesis and structure-activity relationship studies of IgG-binding peptides focused on the C-terminal histidine residue.

Currently, IgG-binding peptides are widely utilized as a research tool, as molecules that guide substrates to the Fc site for site-selective antibody modification, leading to preparation of a homogeneous antibody-drug conjugate. In this study, a structure-activity relationship study of an IgG-binding peptide, 15-IgBP, that is focused on its C-terminal His residue was performed in an attempt to create more potent peptides. A peptide with a substitution of His17 by 2-pyridylalanine (2-Pya) showed a good binding affinity (15-His17(2-Pya), = 75.

Kinetics-Based Structural Requirements of Human Immunoglobulin G Binding Peptides.

Currently, antibodies are widely used not only in research but also in therapy. Hence, peptides that selectively bind to the fragment crystallizable site of an antibody have been extensively utilized in various research efforts such as the preparation of antibody-drug conjugates (ADC). Consequently, appropriate peptides that bind to immunoglobulin G (IgG) with a specific value and also and values will be useful in different applications, and these kinetic parameters have been perhaps overlooked but are key to development of peptide ligands with advantageous binding properties.

Efficient Screening and Design of Variable Domain of Heavy Chain Antibody Ligands Through High Throughput Sequencing for Affinity Chromatography to Purify Fab Fragments.

To design an affinity ligand for purification of antigen-binding fragment (Fab) antibody, variable domain of heavy chain antibody (VHH) phage libraries were constructed from Fab-immunized Alpaca and subjected to biopanning against Fabs. To find the specific binders, we directly applied high-throughput sequencing (HTS) analysis of the VHH sequences in the panned phages on next-generation sequencer. The efficiently enriched sequences were aligned for construction of the phylogenetic tree to be categorized into five groups.

A new technology for increasing therapeutic protein levels in the brain over extended periods.

Effective delivery of protein therapeutics into the brain remains challenging because of difficulties associated with crossing the blood-brain barrier (BBB). To overcome this problem, many researchers have focused on antibodies binding the transferrin receptor (TfR), which is expressed in endothelial cells, including those of the BBB, and is involved in receptor-mediated transcytosis (RMT). RMT and anti-TfR antibodies provide a useful means of delivering therapeutics into the brain, but the anti-TfR antibody has a short half-life in blood because of its broad expression throughout the body.

Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format.

Artificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc.

Prostaglandin E potentiates interferon-γ-induced nitric oxide production in cultured rat microglia.

Prostaglandin E (PGE ) plays crucial roles in managing microglial activation through the prostanoid EP receptor, a PGE receptor subtype. In this study, we report that PGE enhances interferon-γ (IFN-γ)-induced nitric oxide production in microglia. IFN-γ increased the release of nitrite, a metabolite of nitric oxide, which was augmented by PGE , although PGE by itself slightly affects nitrite release.

Formation of three-way scanning electron microscope moiré on micro/nanostructures.

Three-way scanning electron microscope (SEM) moiré was first generated using a designed three-way electron beam (EB) in an SEM. The spot-type three-way SEM moiré comes from the interference between the three-way EB and the specimen grating in which the periodic cells are arranged in a triangular manner. The deformation and the structure information of the specimen grating in three directions can be simultaneously obtained from the three-way SEM moiré.

Spot moiré fringes: determination of domain boundaries and structural parameters in ordered nanoporous structures.

Spot moiré fringes are generated by the superposition between a nanoporous structure and a digital three-way grating. The spot moiré fringes are useful for the characterization of the domain boundaries and structural parameters in ordered nanoporous materials. The pitches and the orientations of the nanopore arrays in three directions can be simultaneously determined in a large view field.

Formation of secondary Moiré patterns for characterization of nanoporous alumina structures in multiple domains with different orientations.

We first report the formation of secondary Moiré patterns from electron Moiré fringes to characterize nanostructures in multiple domains with different orientations. The pitches and the orientations of the nanoporous alumina arrays in several domains are simultaneously measured using only one electron Moiré image.

Three-directional structural characterization of hexagonal packed nanoparticles by hexagonal digital moiré method.

We present the hexagonal digital moiré method for three-directional structural characterization of hexagonal packed nanostructures. A mismatch between a three-way grating and a nanoparticle assembly is shown to produce hexagonal moiré fringes due to the interference between three groups of parallel moiré patterns. The measuring principles of the pitches and the orientations of the three 1D arrays of the nanoparticles are presented.

The exploration of domain sizes and orientation directions in ordered assembled nanoparticles with electron Moiré fringes.

Structural information such as domain sizes and orientation directions in ordered assembled nanoparticles can be simultaneously obtained by using generated electron Moiré fringes, without direct observation of the nanoparticles.

Fabrication of micromodel grid for various moiré methods by femtosecond laser exposure.

The femtosecond laser exposure system was used to fabricate model grids for the charge-coupled device (CCD) moiré method, scanning laser moiré method, and electron moiré method for microstrain deformation measurements. The femtosecond laser exposure produces mesoscopic variation patterns on the surface. These variation patterns make the grid in the scanning laser microscope and CCD images darker and make the grid in the scanning electron microscope image brighter.

Study of the surface structure of butterfly wings using the scanning electron microscopic moiré method.

Scanning electron microscopic (SEM) moiré method was used to study the surface structure of three kinds of butterfly wings: Papilio maackii Menetries, Euploea midamus (Linnaeus), and Stichophthalma howqua (Westwood). Gratings composed of curves with different orientations were found on scales. The planar characteristics of gratings and some other planar features of the surface structure of these wings were revealed, respectively, in terms of virtual strain.