ABSTRACT
Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Subject(s)
Animals , Female , Humans , Antibodies, Bispecific , Allergy and Immunology , Antibodies, Monoclonal , Allergy and Immunology , Pharmacokinetics , CD3 Complex , Metabolism , Cell Line, Tumor , Cytotoxicity, Immunologic , ErbB Receptors , Metabolism , Lymphocyte Activation , Allergy and Immunology , Mice, SCID , Neoplasms , Allergy and Immunology , Pathology , Rats, Sprague-Dawley , T-Lymphocytes, Cytotoxic , Allergy and ImmunologyABSTRACT
OBJECTIVE@#To summarize pseudocyst of auricle governor square included surgical curative effect, the advantages of the analysis of the operation.@*METHOD@#The governor of the central square in auricle pseudocyst incision, 56 cases were retrospectively analyzed clinical data, surgical curative effect and advantages were summarized.@*RESULT@#Adopt the auricle pseudocyst governor of the central square of incision, postoperative follow-up of 6 months did not relapse.@*CONCLUSION@#Rectangle window method effective method of treating pseudocyst of auricle, able to cure pseudocyst of auricle, is a kind of simple, practical, and value in the basic-level hospital surgical method.
Subject(s)
Humans , Cysts , General Surgery , Ear Auricle , Pathology , Ear Diseases , General Surgery , Otologic Surgical Procedures , Methods , Postoperative Period , Retrospective StudiesABSTRACT
AIM: To explore the cellular mechanisms by which GLP-1(7-36)NH 2 stimulates insulin secretion in ?-cells. METHODS: Using adherent cell analysis and sorting cytometer (ACAS) by DiBAC 4(3) as a probe,effects of glucagon-like peptide-1(7-36)NH 2 on membrane potential was investigated in cultured neonatal rat pancreatic islet ?-cells,and radio immunological methods were used to determine the amount of insulin secretion in different glucose concentrations. RESULTS: In the presence of 2.8 mmol/L glucose,GLP-1(7-36)NH 2 could not increase insulin secretion and could not change membrane potentials of ?-cells;In the presence of 5.6,16.7 mmol/L glucose,GLP-1(7-36)NH 2 produced a marked increase in insulin secretion and enhanced the depolarization of ?-cells.In 16.7 mmol/L glucose, EGTA or nifedipine completely blocked GLP-1(7-36)NH 2-induced insulin secretion and changes in membrane potentials of ?-cells. CONCLUSION: GLP-1(7-36)NH 2 stimulates insulin secretion in a glucose concentration-dependent manner,it can enhance the depolarization of ?-cells caused by glucose.