Corrigendum: Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3-mediated therapeutics.

This corrects the article DOI: 10.1038/srep45839.

Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3-mediated therapeutics.

T cell-mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent. In this study we have succeeded in establishing a novel mouse strain in which all the three components of the Cd3 complex - Cd3ε, Cd3δ, and Cd3γ - are replaced by their human counterparts, CD3E, CD3D, and CD3G. Basic immunological assessments have confirmed that this strain of human CD3 EDG-replaced mice are entirely immune competent, and we have also demonstrated that a bispecific antibody that simultaneously binds to human CD3 and a tumor-associated antigen (e.g. ERBB2 or GPC3) can be evaluated in human CD3 EDG-replaced mice engrafted with tumors. Our mouse model provides a novel means to evaluate the in vivo efficacy of human CD3-mediated therapy.

Development of a method for estimating oesophageal temperature by multi-locational temperature measurement inside the external auditory canal.

We aimed to develop a practical method to estimate oesophageal temperature by measuring multi-locational auditory canal temperatures. This method can be applied to prevent heatstroke by simultaneously and continuously monitoring the core temperatures of people working under hot environments. We asked 11 healthy male volunteers to exercise, generating 80 W for 45 min in a climatic chamber set at 24, 32 and 40 °C, at 50% relative humidity. We also exposed the participants to radiation at 32 °C. We continuously measured temperatures at the oesophagus, rectum and three different locations along the external auditory canal. We developed equations for estimating oesophageal temperatures from auditory canal temperatures and compared their fitness and errors. The rectal temperature increased or decreased faster than oesophageal temperature at the start or end of exercise in all conditions. Estimated temperature showed good similarity with oesophageal temperature, and the square of the correlation coefficient of the best fitting model reached 0.904. We observed intermediate values between rectal and oesophageal temperatures during the rest phase. Even under the condition with radiation, estimated oesophageal temperature demonstrated concordant movement with oesophageal temperature at around 0.1 °C overestimation. Our method measured temperatures at three different locations along the external auditory canal. We confirmed that the approach can credibly estimate the oesophageal temperature from 24 to 40 °C for people performing exercise in the same place in a windless environment.

[Evaluation of Portable Coagulation Analyzer in Comparison with Conventional Hospital Laboratory Instrument with Stratification of International Normalized Ratios by Therapeutic Upper Limit].

Point of care devices have been widely applied to outpatients receiving anticoagulation therapy with warfarin for monitoring prothrombin time-international normalized ratio (PT-INR) regularly. However, accuracy in measurement with the device remains undetermined when PT-INR exceeds therapeutic range. We evaluated the performance of a portable CoaguChek XS coagulation analyzer in comparison with a conventional laboratory method according to therapeutic and supra-therapeutic PT-INR values in cardiac outpatients on oral vitamin K antagonists. All participants were classified into 2 groups on the basis of PT-INR 3.0 by the laboratory method; therapeutic group less than or equal to 3.0 (n=48) and supra-therapeutic group above 3.0 (n=8). The correlation coefficients in therapeutic and in supra-therapeutic groups were r=0.82 and r=0.78, respectively (p<0.05). The difference in PT-INR between the laboratory method and the CoaguChek XS was significantly larger in supra-therapeutic group than therapeutic group (1.03±0.73 versus 0.34±0.26, p=0.042). Our study indicates that CoaguChek XS can be useful handheld coagulation analyzer to determine PT-INR rapidly; however, the device may underestimate PT-INR in supra-therapeutic range.