Tumor Evasion from T Cell Surveillance

An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells

Einfluss der Bordnetznachbildung auf Störfestigkeitsmessverfahren (z.B. BCI) oberhalb 100 MHz

Bei Störfestigkeitsmessungen an Automobilelektronik insbesondere im Frequenzbereich oberhalb 100 MHz kommt es vor, dass Prüflinge (DUTs - Device Under Test) trotz standardisierter Messaufbauten und Messmethoden in einem Labor die Anforderungen einhalten, in einem anderen Labor jedoch nicht. Der Beitrag betrachtet diesen Effekt und kommt zu dem Schluss, dass er vom Einfluss der jeweils eingesetzten Bordnetznachbildung (LISN) verursacht wird. Folgende Themen werden anhand von Prinzipschaltbildern, Abbildungen und Diagrammen eingehend diskutiert: Einsatz von LISNs innerhalb und außerhalb ihrer Spezifikation (Messkette und Messaufbau, Spezifikation und Kalibrierung, Pass/Fail - liegt es am Prüfling oder am Labor?); Impedanz von LISNs und Kabel (Impedanzen von LISNs, Einfluss der Kabel, DUT - Annahmen zur Simulation, Koppelkapazität zwischen DUT und Messtisch); Simulation des Gesamtaufbaus und Simulationsergebnisse (Koppelzangen, Kabel, DUT und Koppelkapazität, Variationen der LISNs)

Controlled release of therapeutic antibody formats

The local administration of antibodies can represent in many cases a significant improvement for antibody-based therapies. The benefits of local delivery include high drug concentrations at the target site, the possibility of lower drug dosing and less systemic drug exposure. Currently, the most relevant delivery sites for therapeutic antibodies are the posterior segments of the eye, mucosal surfaces, the articular joints and the central nervous system (CNS). In addition, the oral and pulmonary route may enable non-invasive systemic antibody delivery. However, local antibody delivery to these sites is characterized by short drug residence times and a low compliance of administration. Controlled release (CR) systems can address these limitations and, thereby, enable and improve local delivery applications by achieving long lasting local drug concentrations, improved efficacy-dosing ratios and reduced treatment-associated side effects. The requirements for CR antibody formulations are more complex compared to conventional CR systems for small molecules, and their development poses an enormous technical challenge. Therefore, the review highlights experiences and challenges gathered in the development of the different CR systems for antibodies to date. Additionally, the unmet technological needs encountered in the field are described. This includes a critical evaluation of the limited capability of various CR systems to preserve antibody stability, delivery site specific considerations, as well as the processability of a CR system with a particular focus on drug loading and injectability. We believe that the success of CR and local delivery approaches could create an enormous added value for patients in the future