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Author(s): Naoki Hosen (corresponding author) [1, 2, 3]; Yukiko Matsunaga [4]; Kana Hasegawa [1]; Hiroshi Matsuno [5]; Yuki Nakamura [1]; Mio Makita [1]; Kouki Watanabe [1]; Mikako Yoshida [1]; Kei [...], Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM). We screened [greater than] 10,000 anti-MM mAb clones and identified MMG49 as an MM-specific mAb specifically recognizing a subset of integrin [beta][sub.7] molecules. The MMG49 epitope, in the N-terminal region of the [beta][sub.7] chain, is predicted to be inaccessible in the resting integrin conformer but exposed in the active conformation. Elevated expression and constitutive activation of integrin [beta][sub.7] conferred high MMG49 reactivity on MM cells, whereas MMG49 binding was scarcely detectable in other cell types including normal integrin [beta][sub.7][sup.+] lymphocytes. T cells transduced with MMG49-derived chimeric antigen receptor (CAR) exerted anti-MM effects without damaging normal hematopoietic cells. Thus, MMG49 CAR T cell therapy is promising for MM, and a receptor protein with a rare but physiologically relevant conformation can serve as a cancer immunotherapy target.

Background: Assessing the presence of pharyngeal residue in the pyriform sinus and epiglottic vallecula is important because insufficient pharyngeal clearance is a risk factor for aspiration pneumonia. Improvements in the performance of ultrasound to visualize the pyriform sinus and epiglottic vallecula are needed. The aim of this study was to establish a method to visualize the pyriform sinus and epiglottic vallecula with ultrasound to detect pharyngeal residue., Methods: We used real-time virtual sonography (ie, a fusion of magnetic resonance imaging and ultrasound imaging) as the scanning method to visualize the pyriform sinus and epiglottic vallecula without residue in 4 healthy individuals. Using established ultrasound methodology and fiberoptic endoscopic evaluation of swallowing, 35 subjects with dysphagia were studied to investigate the performance of ultrasound to detect pharyngeal residue., Results: The fusion ultrasound images showed that transverse scans at the level of the laryngeal prominence and above the hyoid bone using a linear array transducer can be used to visualize the pyriform sinus and the epiglottic vallecula, respectively. We obtained 238 ultrasound images of the pyriform sinus from 35 subjects and 82 images of epiglottic vallecula from 26 of 35 subjects. The ultrasound images with fiberoptic endoscopic evaluation of swallowing showed that areas of high echogenicity in the pyriform sinus and epiglottic vallecula are related to the presence of pharyngeal residue. The presence of high-echogenicity areas resulted in a sensitivity of 92.0% and specificity of 71.9% for detecting pharyngeal residue in the pyriform sinus and a sensitivity of 86.7% and specificity of 63.6% for detecting pharyngeal residue in the epiglottic vallecula., Conclusions: Transverse ultrasound scans at the level of the laryngeal prominence and above the hyoid bone enable the visualization of the pyriform sinus, epiglottic vallecula, and pharyngeal residue., (Copyright © 2020 by Daedalus Enterprises.)

Wound blotting can be used to visualize the protein distribution on a wound bed through protein collection by attaching a nitrocellulose membrane to the wound surface. This study checked for consistency between the protein distributions determined by wound blotting and those determined by removal of the tissue. A patient who was planning to undergo surgical debridement of an ulcer in the sacral region that was caused by lying down for a long period after a cerebral hemorrhage was recruited in Fujisawa City Hospital, Kanagawa, Japan. Wound blotting was performed just prior to surgical debridement and the debrided tissue embedded in paraffin. The ulcer, which had a 2.9 cm major axis, was divided into 20 areas approximately 0.35 cm2 each, and the consistency of tumor necrosis factor-α positivity between the wound blotting samples and tissue sections was examined in each area. The sensitivity and specificity of wound blotting were 89% and 82%, respectively. This wound blotting method noninvasively revealed the protein distributions within the wound tissue.