Novel Antibody Exerts Antitumor Effect through Downregulation of CD147 and Activation of Multiple Stress Signals.

CD147 is an immunoglobulin-like receptor that is highly expressed in various cancers and involved in the growth, metastasis, and activation of inflammatory pathways via interactions with various functional molecules, such as integrins, CD44, and monocarboxylate transporters. Through screening of CD147-targeting antibodies with antitumor efficacy, we discovered a novel rat monoclonal antibody 147D. This humanized IgG4-formatted antibody, h4147D, showed potent antitumor efficacy in xenograft mouse models harboring the human PDAC cell line MIA PaCa-2, HCC cell line Hep G2, and CML cell line KU812, which featured low sensitivity to the corresponding standard-of-care drugs (gemcitabine, sorafenib, and imatinib, respectively).

Preparation and Photocatalytic Activity of Hexagonal Plate-like ZnO Particles Using Anionic Surfactants.

Hexagonal plate-like ZnO particles with a high degree of c-face orientation have been synthesized using hydrothermal method in the presence of various anionic surfactants bearing different hydrocarbon chains. The c-face of the ZnO particles increased upon increasing the surfactant alkyl chain length. The photocatalytic activity of the as-obtained hexagonal plate-like ZnO particles was evaluated using the degradation of methylene blue (MB).

Synthesis and Photocatalytic Activity of Hexagonal Plate-like Shaped Au Nanoparticles/ZnO Composite Particles under Visible-light Irradiation.

We synthesized Au nanoparticle (AuNP)/ZnO composite particles in presence of an anionic surfactant and evaluated their photocatalytic activity under visible-light irradiation. AuNPs synthesized from HAuCl in the presence of amylase and the precursor solutions of ZnO were mixed, followed by a hydrothermal process, to synthesize crystal face-controlled AuNP/ZnO composite particles. X-ray diffraction (XRD) patterns and ultraviolet-visible (UV-Vis) spectra confirmed the formation of AuNP/ZnO composite particles.

Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans.

Effect of Anionic Amphiphiles on the Morphology of Hexagonal Plate-like ZnO Particles.

Zinc oxide (ZnO) particles were synthesized in the presence of anionic surfactants (ASs). The effect of ASs on the morphology of the ZnO particles was investigated by using ASs with various alkyl chain lengths and changing the molar ratio of AS/ZnSO. Hexagonal plate-like ZnO particles were formed in the presence of ASs.

Preparation of Hexagonal Plate-like ZnO Single-crystal Particles in the Presence of Anionic Amphiphiles.

In this study, we synthesized ZnO particles using anionic amphiphiles as an additive. While the single-crystal particles prepared in the absence of such amphiphiles had a hexagonal rod-like shape, those fabricated using anionic amphiphilic molecules had a hexagonal plate-like shape. The anionic amphiphiles inhibited crystal growth in the c-axis direction of ZnO.

Suppression of Methionine Oxidation of a Pharmaceutical Antibody Stored in a Polymer-Based Syringe.

Oxidation of methionine residues is one of the well-known deteriorations in monoclonal antibody (mAb) therapeutics. Because methionine oxidation may affect their efficacy and pharmacokinetic profile, oxidation levels should be strictly controlled during their storage period. In this study, we revealed that when a therapeutic antibody was filled into a cyclo olefin polymer-based syringe and stored in a blister pack with an oxygen absorber, the methionine oxidation production under thermal or light stress was suppressed because of the reduction in the concentration of dissolved oxygen.

Detection of histidine oxidation in a monoclonal immunoglobulin gamma (IgG) 1 antibody.

Although oxidation of methionine and tryptophan are known as popular chemical modifications that occur in monoclonal antibody (mAb) molecules, oxidation of other amino acids in mAbs has not been reported to date. In this study, oxidation of the histidine residue in a human immunoglobulin gamma (IgG) 1 molecule was discovered for the first time by mass spectrometry. The oxidation of a specific histidine located at the CH2 domain of IgG1 occurred under light stress, but it was not observed under heat stress.

Specific racemization of heavy-chain cysteine-220 in the hinge region of immunoglobulin gamma 1 as a possible cause of degradation during storage.

Therapeutic antibodies often suffer from degradation due to various modifications during storage. We detected a degradation of immunoglobulin gamma 1 (IgG1) stored for 6 month at 40 °C, and identified the modification as the racemization of Cys220 in the hinge sequence S(219)CDKTHT(225) of the heavy chain by tryptic peptide mapping and tandem mass spectrometry. The rate of racemization at Cys220 was enhanced deliberately by incubating the protein at 50 °C and pH 9.