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In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgAl-E), and the effect of mAb binding valency on FcγRI-mediated ADCC. All hybrid monospecific (ms) anti-HulgAl and bispecific (bs) anti-HuIgA1/HRP mAb were capable of inducing monocyte-mediated lysis of HuIgAl-E, in spite of differences in mAb densities essential for optimal lysis. The cytotoxicity induced by hybrid mAb which consist of one or more mlgG2a H chains was predominantly mediated via FcγRI, as shown by inhibition studies on monocytes with FcγRI-blocking mAb TB-3 (≈80% inhibition). However, partial inhibition of mtgGl-2a and mlgG2a-2b-induced cytotoxicity (20-50%) was observed by using FcγRll-blocking mAb IV.3 or CIKM5. For hybrid mIgGl-l mAb the opposite was true; the cytotoxicity was predominantly mediated via FcαRlI (70-80%) and less via FcγRl (20-30%). Comparing the hybrid ms anti-HulgA 1 mAb-induced cytotoxicity with the cytotoxicity induced by hybrid bs anti-HuIgAl/HRP mAb of the same isotype, we observed a decrease in cytotoxicity towards HuIgAl-E sensitized with univalently bound bs anti-HuIgAl/HRP mAb. This decrease was only found for FcγRI-mediated ADCC (mlgG2ae2a, mlgGl -2a and mIgG2a-2b). This diminished recognition of univalently bound IgG relative to bivalently bound IgC by FcγRI was also observed with U937 effector cells. In conclusion, this work shows that hybrid mAb are able to induce monocyte-mediated cytotoxicity towards E-HuIgA1 and that there appears to be an effect of Ag-IgG binding valency on FcγRI-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Background: There is a lack of standardized mobility measures specific to the long-term care (LTC) population. Therefore, the Continuing Care Activity Measure (CCAM) was developed., Objective: This study determined levels of reliability, validity for clinical utilization, and sensitivity to change of this measure., Design: This was a prospective longitudinal cohort study among elderly people with primarily physical or medical impairments who were residing in LTC institutions that provide nursing home and more-complex care, with access to physical therapy services., Method: The CCAM, the Clinical Outcome Variables Scale (COVS), the Social Engagement Scale (SES) of the Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0 instrument, and the Resource Utilization Groups, version 3, (RUG-III) were administered by clinical and research physical therapists, with timing dictated by the study purpose., Results: The participants were 136 residents of LTC institutions and 21 physical therapists. The CCAM interrater reliability (intraclass correlation coefficient [ICC]) was .97 (95% confidence interval=.91-1.00), and test-retest reliability (ICC) over a period of 1 week was .99 (95% confidence interval=.93-1.00). Over 6 months, the absolute change in total score was 5.88 for the CCAM and 4.26 for the COVS; the CCAM was 28% more responsive across all participants (n=105) and 68% more responsive for those scoring in the lower half (n=49). The minimal detectable difference of the CCAM was 8.6 across all participants. The CCAM correlated with the COVS, nursing care hours inferred from the RUG-III, and the SES., Limitations: Some participants were lost to follow-up., Conclusions: The CCAM is a reliable and valid tool to measure gross motor function and physical mobility for elderly people in LTC institutions. It discriminates among functional levels, measures individual functional change, and can contribute to clinical decision making.

In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgA1-E), and the effect of mAb binding valency on Fc gamma RI-mediated ADCC. All hybrid monospecific (ms) anti-HuIgA1 and bispecific (bs) anti-HuIgA1/HRP mAb were capable of inducing monocyte-mediated lysis of HuIgA1-E, in spite of differences in mAb densities essential for optimal lysis. The cytotoxicity induced by hybrid mAb which consist of one or more mIgG2a H chains was predominantly mediated via Fc gamma RI, as shown by inhibition studies on monocytes with Fc gamma RI-blocking mAb TB-3 (approximately 80% inhibition). However, partial inhibition of mIgG1-2a and mIgG2a-2b-induced cytotoxicity (20-50%) was observed by using Fc gamma RII-blocking mAb IV.3 or CIKM5. For hybrid mIgG1-1 mAb the opposite was true; the cytotoxicity was predominantly mediated via Fc gamma RII (70-80%) and less via Fc gamma RI (20-30%). Comparing the hybrid ms anti-HuIgA1 mAb-induced cytotoxicity with the cytotoxicity induced by hybrid bs anti-HuIgA1/HRP mAb of the same isotype, we observed a decrease in cytotoxicity towards HuIgA1-E sensitized with univalently bound bs anti-HuIgA1/HRP mAb. This decrease was only found for Fc gamma RI-mediated ADCC (mIgG2a-2a, mIgG1-2a and mIgG2a-2b). This diminished recognition of univalently bound IgG relative to bivalently bound IgG by Fc gamma RI was also observed with U937 effector cells. In conclusion, this work shows that hybrid mAb are able to induce monocyte-mediated cytotoxicity towards E-HuIgA1 and that there appears to be an effect of Ag-IgG binding valency on Fc gamma RI-mediated cytotoxicity.