Anti-tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models.

Antibody-drug conjugates (ADCs) have been recognized as a promising class of cancer therapeutics. Tissue factor (TF), an initiator of the blood coagulation pathway, has been investigated regarding its relationship with cancer, and several preclinical and clinical studies have presented data on anti-TF ADCs, including tisotumab vedotin, which was approved in 2021. However, the feasibility of other payloads in the design of anti-TF ADCs is still unclear because no reports have compared payloads with different cytotoxic mechanisms.

Tumor Targeting of At-Labeled Antibody under Sodium Ascorbate Protection against Radiolysis.

Astatine-211 (At) is an alpha emitter applicable to radioimmunotherapy (RIT), a cancer treatment that utilizes radioactive antibodies to target tumors. In the preparation of At-labeled monoclonal antibodies (At-mAbs), the possibility of radionuclide-induced antibody denaturation (radiolysis) is of concern. Our previous study showed that this At-induced radiochemical reaction disrupts the cellular binding activity of an astatinated mAb, resulting in attenuation of antitumor effects, whereas sodium ascorbate (SA), a free radical scavenger, prevents antibody denaturation, contributing to the maintenance of binding and antitumor activity.

Identification of CD73 as the Antigen of an Antigen-Unknown Monoclonal Antibody Established by Exosome Immunization, and Its Antibody-Drug Conjugate Exerts an Antitumor Effect on Glioblastoma Cell Lines.

Development of antibodies against the native structure of membrane proteins with multiple transmembrane domains is challenging because it is difficult to prepare antigens with native structures. Previously, we successfully developed a monoclonal antibody against multi-pass membrane protein TMEM180 by exosome immunization in rats. This approach yielded antibodies that recognized cancer-specific antigens on the exosome.

Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy.

Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose.

TMEM180 contributes to SW480 human colorectal cancer cell proliferation through intra-cellular metabolic pathways.

TMEM180, a novel colon cancer-specific protein with a 12-transmembrane topology, is upregulated at low oxygen. Previously, we established a humanized monoclonal antibody against TMEM180 aimed at clinical trials. Prior to such trials, it is necessary to clarify the function of TMEM180 in cancer.

Radioimmunotherapy with an At-labeled anti-tissue factor antibody protected by sodium ascorbate.

Tissue factor (TF), the trigger protein of the extrinsic blood coagulation cascade, is abundantly expressed in various cancers including gastric cancer. Anti-TF monoclonal antibodies (mAbs) capable of targeting cancers have been successfully applied to armed antibodies such as antibody-drug conjugates (ADCs) and molecular imaging probes. We prepared an anti-TF mAb, clone 1084, labeled with astatine-211 ( At), as a promising alpha emitter for cancer treatment.

Antitumor effect of humanized anti‑tissue factor antibody‑drug conjugate in a model of peritoneal disseminated pancreatic cancer.

Tissue factor (TF) is an attractive target for cancer therapy due to its overexpression in multiple types of malignancies. In addition, TF has been reported to play functional roles in both cancer development and metastasis. Several groups have already developed antibody‑drug conjugates (ADCs) against TF for use as cancer treatments, and have demonstrated their efficacies in conventional subcutaneous xenograft models and patient‑derived xenograft models.

Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor.

MCFD2 and ERGIC-53, which are the products of causative genes of combined factor V and factor VIII deficiency, form a cargo receptor complex responsible for intracellular transport of these coagulation factors in the early secretory pathway. In this study, using an NMR technique, we successfully identified an MCFD2-binding segment from factor VIII composed of a 10 amino acid sequence that enhances its secretion. This prompted us to examine possible effects of attaching this sequence to recombinant glycoproteins on their secretion.

Topological analysis of TMEM180, a newly identified membrane protein that is highly expressed in colorectal cancer cells.

New target molecules for diagnosis of and drug development for colorectal cancer (CRC) are always in great demand. Previously, we identified a new colorectal cancer-specific protein, TMEM180, and successfully developed an anti-TMEM180 monoclonal antibody (mAb) for the diagnosis and treatment of CRC. Although TMEM180 is classified as a member of the cation symporter family and multi-pass membrane protein, little is known about its function.

EVALUATION AND STATISTICAL ANALYSIS OF THE USE OF INFOGRAPHICS IN RADIOLOGY EDUCATION.

Interest in the need for systematic radiology education has increased since the Fukushima Daiichi nuclear disaster. Practice and attitude surveys on radiology education have been previously undertaken and indicate that there is currently limited quantitative knowledge on the use of radiation and radiological consequences. Although maintenance of an education system and measurements of its effects on knowledge levels have been conducted, no novel developments have been made in the methods of measurement.

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer-specific molecule.

The present state of therapy for colorectal cancer (CRC) is far from satisfactory, highlighting the need for new targets for this disease. We identified a new CRC-specific molecule, TMEM180, a predicted 11-pass transmembrane protein that apparently functions as a cation symporter. We developed an anti-TMEM180 mAb and then succeeded in humanizing the mAb.

Redox-coupled structural changes of the catalytic a' domain of protein disulfide isomerase.

Protein disulfide isomerase functions as a folding catalyst in the endoplasmic reticulum. Its b' and a' domains provide substrate-binding sites and undergo a redox-dependent domain rearrangement coupled to an open-closed structural change. Here we determined the first solution structure of the a' domain in its oxidized form and thereby demonstrate that oxidation of the a' domain induces significant conformational changes not only in the vicinity of the active site but also in the distal b'-interfacial segment.

Crystallization behavior of single isotactic poly(methyl methacrylate) chains visualized by atomic force microscopy.

We have, for the first time, successfully visualized the crystallization behavior of a single isolated polymer chain at the molecular level by atomic force microscopy (AFM). Previously, we found that isotactic poly(methyl methacrylate) (it-PMMA) formed two-dimensional folded chain crystals composed of double-stranded helices upon compression of its Langmuir monolayer on a water surface, and the molecular images of the crystals deposited on mica were clearly visualized by AFM (Kumaki, J.; et al.

NMR analyses on the interactions of the yeast Tim50 C-terminal region with the presequence and Tim50 core domain.

The mitochondrial targeting signal in the presequence of mitochondrial precursor proteins is recognized by Tom20 and subsequently by Tim50 in mitochondria. Yeast Tim50 contains two presequence binding sites in the conserved core domain and in the fungi-specific C-terminal presequence binding domain (PBD). We report the NMR analyses on interactions of a shorter variant of PBD (sPBD), a shorter variant of PBD, with presequences.