Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.
Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.
BACKGROUND Arterial catheters are potential sources of nosocomial infection. OBJECTIVE To investigate use of a closed blood conservation device in preventing catheter-related bloodstream infections in children after cardiac surgery. METHODS Children with an indwelling arterial catheter after cardiac surgery were randomly assigned to 2 groups: a control group with a conventional 3-way stopcock in the catheter system and an interventional group with the conservation device in the catheter system. Catheter tips, catheter intraluminal fluid, and blood samples obtained from the catheter and peripherally were cultured for microbiological analysis. RESULTS Intraluminal fluid contamination was significantly lower (P = .03) in the interventional group (3 of 147 catheters) than in the control group (10 of 137 catheters). The 2 groups did not differ significantly in the rate of tip colonization (9 of 147 vs 12 of 137; P = .40) or in the number of catheter-related bloodstream infections (0 of 147 vs 2 of 137; P = .21). CONCLUSION Use of a closed blood conservation device could decrease the incidence of catheter-related contamination of intraluminal fluid. (Critical Care Nurse. 2014;34[5]:53-61)
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