Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo.

The SARS-CoV-2 pandemic alerted the potential for significant harm due to future cross-species transmission of various animal coronaviruses to human. There is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. In this study, we generated CV804, an antibody that binds to the S2 domain of SARS-CoV-2 spike protein, which is highly conserved across the coronavirus family and less susceptible to mutations.

S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells.

Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating Tregs is, therefore, expected to activate antitumor immunity without affecting immune homeostasis. We previously reported that selective Treg depletion targeted by a C-C motif chemokine receptor 8 (CCR8) resulted in induction of strong antitumor immunity without any obvious autoimmunity in mouse models.

CD62L expression marks SARS-CoV-2 memory B cell subset with preference for neutralizing epitopes.

Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (B) cells have variation in the neutralizing activities. Here, by combining single B cell profiling with antibody functional assessment, we dissected the phenotype of B cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals.

CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory.

Foxp3-expressing CD25CD4 regulatory T cells (Tregs) are abundant in tumor tissues. Here, hypothesizing that tumor Tregs would clonally expand after they are activated by tumor-associated antigens to suppress antitumor immune responses, we performed single-cell analysis on tumor Tregs to characterize them by T cell receptor clonotype and gene-expression profiles. We found that multiclonal Tregs present in tumor tissues predominantly expressed the chemokine receptor CCR8.

Sjögren's syndrome concurrent with protein-losing gastroenteropathy with secondary systemic capillary leak syndrome : A case report.

Sjögren's syndrome concurrent with protein-losing gastroenteropathy can develop into secondary systemic capillary leak syndrome. Thus, it is important to diagnose the condition as soon as possible and simultaneously administer treatment for Sjögren's syndrome, protein-losing gastroenteropathy, and systemic capillary leak syndrome.

Double "Open and Shut" Transformation of γ-Carbolines Triggered by Ammonium Salts: One-Pot Synthesis of Multiheterocyclic Compounds.

A novel cascade reaction of indole-2,3-epoxide equivalents with γ-carbolines by utilizing a double "open and shut" transformation to access multiheterocyclic compounds containing both isotryptamines and pyrimido[1,6- a]indoles has been developed. This strategy utilizes the in situ formation of a bulky quaternary ammonium salt via ammonium exchange, which undergoes Hofmann elimination/vinylogous Mannich/retro-Mannich/cyclization cascade sequences.

Synthesis and in vitro evaluation of radioiodinated indolequinones targeting NAD(P)H: quinone oxidoreductase 1 for internal radiation therapy.

quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([(125)I]1 and [(125)I]2) and a sulfide linkage compound ([(125)I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect.

Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody.

Monoclonal antibodies (mAbs) that are internalized into cells are a current focus in the development of antibody-drug conjugates (ADCs). We describe a phage display-based high-throughput screening system to rapidly isolate cell-internalizing mAbs. We simultaneously examined the cell-internalizing activities of several hundred independent mAbs and successfully isolated cell-internalizing mAbs against the tumor endothelial markers Roundabout homolog 4 (Robo4) and vascular endothelial growth factor receptor 2 (VEGFR2).

Induction of endoplasmic reticulum-endosome fusion for antigen cross-presentation induced by poly (γ-glutamic acid) nanoparticles.

We previously reported that poly (γ-glutamic acid)-based nanoparticles (γ-PGA NPs) are excellent vaccine carriers for inducing efficient cross-presentation in dendritic cells, thereby producing strong antitumor immunity in vivo. Analyzing the mechanism of cross-presentation induced by γ-PGA NPs will be useful toward designing novel vaccine carriers. In this study, we show an intracellular mechanism of efficient cross-presentation induced by OVA-loaded γ-PGA NPs.

Adaptive evolution of sexual systems in pedunculate barnacles.

How and why diverse sexual systems evolve are fascinating evolutionary questions, but few empirical studies have dealt with these questions in animals. Pedunculate (gooseneck) barnacles show such diversity, including simultaneous hermaphroditism, coexistence of dwarf males and hermaphrodites (androdioecy), and coexistence of dwarf males and females (dioecy). Here, we report the first phylogenetically controlled test of the hypothesis that the ultimate cause of the diverse sexual systems and presence of dwarf males in this group is limited mating opportunities for non-dwarf individuals, owing to mating in small groups.

Modifying the antigen-immunization schedule improves the variety of monoclonal antibodies obtained from immune-phage antibody libraries against HIV-1 Nef and Vif.

Immune phage antibody libraries are an attractive technology for isolating antigen-specific monoclonal antibodies (mAbs). Here we show that the immunization schedule affects the immune phage antibody library properties. We subcutaneously (s.

Solution of the structure of the TNF-TNFR2 complex.

Tumor necrosis factor (TNF) is an inflammatory cytokine that has important roles in various immune responses, which are mediated through its two receptors, TNF receptor 1 (TNFR1) and TNFR2. Antibody-based therapy against TNF is used clinically to treat several chronic autoimmune diseases; however, such treatment sometimes results in serious side effects, which are thought to be caused by the blocking of signals from both TNFRs. Therefore, knowledge of the structural basis for the recognition of TNF by each receptor would be invaluable in designing TNFR-selective drugs.

[Successful treatment of interstitial pneumonia and pneumomediastinum associated with polymyositis during pregnancy with a combination of cyclophosphamide and tacrolimus: A case report].

A 30-year-old pregnant woman experienced mild dyspnea in April 2009. She complained of mild myalgia and was subsequently admitted to our hospital in June 2009 because of worsening dyspnea. Physical examination revealed fine crackles in the lower lung field, but no eruptions externally.

Simple PEG conjugation of SPIO via an Au-S bond improves its tumor targeting potency as a novel MR tumor imaging agent.

Gold/iron oxide magnetic nanoparticles are hybrid nanoparticles containing a core of magnetic iron oxide and surface colloidal gold, which allows for various biomaterials to be immobilized on the surface of the iron oxide nanoparticles via colloidal gold. Here, we developed a novel magnetic resonance (MR) imaging agent to broaden the MR tumor-imaging spectrum of superparamagnetic iron oxide nanoparticles (SPIO), e.g.

Direct cell entry of gold/iron-oxide magnetic nanoparticles in adenovirus mediated gene delivery.

Gold/iron-oxide MAgnetic Nanoparticles (GoldMAN) imparts useful magnetic properties to various biomolecules. Gold nanoparticles immobilized on the surface of magnetic nanoparticles allow for the conjugation of biomolecules via an Au-S bond. Here, we present a practical application by utilizing GoldMAN and a magnetic field to induce intracellular transduction.

Ligand-independent assembly of purified soluble magic roundabout (Robo4), a tumor-specific endothelial marker.

Magic roundabout (Robo4) is the fourth recently identified member of the roundabout receptor family. Robo4 is predominantly expressed in embryonic or tumor vascular endothelium and is considered important for vascular development and as a candidate tumor endothelial marker. Much remains unknown about the Robo4 molecule, however, such as its ligands, structure, and the details of its function.

Pyridinium cationic-dimer antimalarials, unlike chloroquine, act selectively between the schizont stage and the ring stage of Plasmodium falciparum.

Malaria is a leading cause of death in developing countries, and the emergence of strains resistant to the main therapeutic agent, chloroquine, has become a serious problem. We have developed cationic-dimer type antimalarials, MAP-610 and PMAP-H10, which are structurally different from chloroquine. In this study, we introduced several substituents on the terminal phenyl rings of PMAP-H10.

Antimalarial cation-dimers synthesized in two steps from an inexpensive starting material, isonicotinic acid.

Malaria is one of the three major serious infectious diseases in the world. As the area affected by malaria includes a large proportion of developing countries, there is a need for new antimalarials that can be synthesized and supplied inexpensively. To generate low-cost antimalarials, the MAP series 6-10, bis-cation dimers, synthesized by amidating the carboxyl group of isonicotinic acid (11) with various amines and by cationizing the nitrogen atoms of the pyridine ring with the corresponding alkyl bromides, were designed.