Sigma-1 receptor (sigma-1R) was cloned in human and several animal species (Hanner et al.

Monoclonal antibody (mAb) drugs offer a number of valuable treatments. Many newly developed mAb drugs include artificial modification of amino acid sequences from human origin, which may cause higher immunogenicity to induce anti-drug antibodies (ADA). If the immunogenicity of a new candidate can be understood in the nonclinical phase, clinical studies will be safer and the success rate of development improved. Empirically, in vitro immunogenicity assays with human cells have proved to be sufficiently sensitive to nonhuman proteins, but not to human/humanized mAb. To detect the weaker immunogenicity of human-based mAb, a more sensitive biomarker for in vitro assays is needed. The in vitro study here developed a proliferation assay (T H cell assay) using flow cytometry analysis that can detect a slight increase in proliferating T H cells. Samples from 218 donors treated with a low-immunogenic drug (etanercept) were measured to determine a positive threshold level. With this threshold, positive donor percentages among PBMC after treatment with higher-immunogenicity mAb drugs were noted, that is, 39.5% with humanized anti-human A33 antibody (hA33), 27.3% with abciximab, 25.9% with adalimumab, and 14.8% with infliximab. Biotherapeutics with low immunogenicity yielded values of 0% for basiliximab and 3.7% for etanercept. These data showed a good comparability with previously reported incidences of clinical ADA with the evaluated drugs. Calculations based on the data here showed that a T H cell assay with 40 donors could provide statistically significant differences when comparing low-(etanercept) versus highly immunogenic mAb (except for infliximab). Based on the outcomes here, for screening purposes, a practical cutoff point of 3/20 positives with 20 donors was proposed to alert immunogenicity of mAb drug candidates.

Mast cells are key players in the inflammatory response with an important role in allergic reactions and are therefore useful for assessing the risk of anaphylaxis. However, they are difficult to isolate due to their low abundance and wide distribution. To overcome this, we generated and characterized mast cell-like cells derived from human induced pluripotent stem (hiPS) cells. These hiPS cell-derived mast cells (hiPS-MCs) were generated using recombinant human bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor 165 (VEGF), stem cell factor (SCF), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-9 (IL-9) in a StemPro-34 medium. The hiPS-MCs exhibited the morphological characteristics of human mast cells, expressing high affinity-IgE receptor (FcεRI) and mast cell markers such as tryptase, chymase, and CD117. In addition, FcεRI stimulation with agonistic anti-IgE functionally increased the expression of activation markers CD63 and CD203c, as well as the amount of released histamine. We think the hiPS-MCs generated in this study will be useful for assessing the pharmacology and toxicity of anti-allergy medicines.

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Influence of Motor Imagery during Cast Immobilization of the Knee Joint on Range of Motion after Cast Removal: a Case Study 中野 英樹 1) 生野 達也 1) 奥埜 博之 1) 川見 清豪 1) 藤田 浩之 2) 吉田 慎一 2) 河村 章史 2) 森岡 周 2) HIDEKO NAKANO 1) , TATSUYA IKUNO 1) , HIROYUKI OKUNO 1) , SEIGOU KAWAMI 1) , HIROYUKI FUJITA 2) , SHINICHI YOSHIDA 2) , AKIFUMI KOUMURA 2) , SHU MORIOKA 2)