Activation of the complement system by tumor cells was long believed to only benefit the host. Overexpression of complement inhibitors by many tumor cell types and results obtained in several experimental animal models were all in agreement with this hypothesis. However, recent reports imply that the situation is more complex than initially believed and that under certain circumstances tumor ce...

The standard method to detect pretransplant antibodies has been the complement dependent cytotoxicity (CDC) test of donor leukocytes. Solid phase assays to detect HLA antibodies in pretransplant serum reveal a greater number of sensitized patients, but their clinical impact is less certain. Here we have developed a method of detecting C4d fixing HLA antibodies on Luminex beads. Pretransplant se...

To develop more effective anti-CD20 reagents for B-cell lymphoma, we designed and constructed a bispecific tetravalent anti-CD20 antibody, 11B8/2F2(ScFvHL)(4)-Fc, derived from two fully human monoclonal antibodies (mAb), 2F2 and 11B8. 2F2 is a type I CD20 mAb, which is potent in complement-dependent cytotoxicity (CDC) assays but poor at inducing apoptosis, whereas 11B8 is a type II CD20 mAb, wh...

The structure of asparagine-linked oligosaccharides attached to the antibody constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, it is still unclear how differences in the N-linked oligosaccharide structures imp...

Some therapeutic antibodies as anticancer agents exert their effects through the host immune system, but the factors that predict their cytotoxicity, including complement-dependent cytotoxicity (CDC), are unclear. In the present study, we attempted to elucidate some of these factors in a preclinical model. CDC-related mesangiolysis caused by administration of the anti-Thy-1.1 antibody can be st...

Establishment of anterior-posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin-myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate t...

Cardiac transplantation remains the best treatment in patients with advanced heart failure with a high risk of death. However, an inadequate supply of donor hearts decreases the likelihood of transplantation for many patients. Ventricular assist devices (VADs) are being increasingly used as a bridge to transplantation in patients who may not survive long enough to receive a heart. This expansio...

Unresponsiveness to rituximab treatment develops in many patients prompting elucidation of underlying molecular pathways. It was recently observed that rituximab-resistant lymphoma cells exhibit up-regulation of components of the ubiquitin-proteasome system (UPS). Therefore, we investigated in more detail the role of this system in the regulation of CD20 levels and the influence of proteasome i...

Antibodies directed against HLA antigens of a given organ donor represent the dominating reason for hyper-acute or acute allograft rejections. In order to select recipients without donor-specific antibodies, a standard crossmatch (CM) procedure, the complement-dependent cytotoxicity assay (CDC), was developed. This functional assay strongly depends on the availability of isolated vital lymphocy...

Background The aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex. Methods This retrospective study included HLA antibody screening resul...