1.Design of next generation antibody drug conjugates.
Acta Pharmaceutica Sinica 2013;48(7):1053-70
Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.
2.Relationship between serum concentrations of IL-18, IL-10, IL-6 and acute coronary syndrome
Wencheng NIE ; Guosheng FU ; Yangxin CHEN ; Geng XU ; Ji MA ; Yuping SHI ; Jiang SHAN
Chinese Journal of Pathophysiology 1989;0(05):-
AIM: To examine the relation between serum concentrations of interleukin-18, interleukin-10, interleukin-6 and acute coronary syndrome (ACS). METHODS: Serum concentrations of IL-18, IL-10, IL-6 were measured in 17 patients with acute myocardial infarction (AMI), 30 patients with unstable angina pectoris (UAP), 15 patients with stable angina pectoris (SAP) and 20 controls by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA).The relation between IL-18, IL-6 and IL-10 was compared. RESULTS: Serum concentrations of IL-18, IL-6 were significantly increased in the AMI and UAP groups in comparison with the SAP and control groups. Conversely, serum concentrations of IL-10 were significantly decreased in the AMI and UAP groups in comparison with the SAP and control groups. The correlation of concentrations of IL-18 and IL-6 had no significance; but the levels of IL-18 and IL-6 were negatively correlated with IL-10. CONCLUSION: Serum IL-18, IL-6 concentrations increase while serum IL-10 concentration decreases in patients with acute coronary syndromes. The inflammatory imbalance between IL-18, IL-6 and IL-10 may play an important role in the instability of atherosclerotic plaque.