Showing papers by "Michael Bachmann published in 2013"
TL;DR: Co-transduced T cells destroy tumors that express both antigens but do not affect tumors expressing either antigen alone, and this 'tumor-sensing' strategy may help broaden the applicability and avoid some of the side effects of targeted T-cell therapies.
Abstract: To increase the tumor specificity of engineered T cells, Kloss et al. design an approach that relies on T cell recognition of two, rather than one, antigens.
746 citations
TL;DR: It is found that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.
Abstract: Legumain is a lysosomal cysteine protease whose biological function remains poorly defined. Legumain activity is up-regulated in most human cancers and inflammatory diseases most likely as the result of high expression in populations of activated macrophages. Within the tumor microenvironment, legumain activity is thought to promote tumorigenesis. To obtain a greater understanding of the role of legumain activity during cancer progression and inflammation, we developed an activity-based probe that becomes fluorescent only upon binding active legumain. This probe is highly selective for legumain, even in the context of whole cells and tissues, and is also a more effective label of legumain than previously reported probes. Here we present the synthesis and application of our probe to the analysis of legumain activity in primary macrophages and in two mouse models of cancer. We find that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.
125 citations
TL;DR: UTX knockdown in zebrafish significantly impairs SDF-1/CXCR4-dependent migration of primordial germ cells, suggesting that UTX is a critical regulator for stem cell migration and hematopoiesis.
97 citations
TL;DR: Redirection of T cells with a first fully humanized bispecific CD33–CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells.
Abstract: Redirection of T cells with a first fully humanized bispecific CD33–CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells
75 citations
TL;DR: It is concluded that slanDCs have molecular and functional features of a pro-inflammatory myeloid DC type relevant for the immunopathogenesis of LE.
74 citations
TL;DR: It is shown that La protein is not limited to the surface of dying cells but will be released upon stress-induced cell death, and a novel fully humanized single-chain bispecific antibody which on the one hand is directed to the La antigen and on the other hand to the CD3 complex of T cells activated Tregs in a target-dependent manner.
55 citations
TL;DR: It is demonstrated that doxorubicin and vinblastine significantly impair the release of tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐12 by slanDCs, and these novel findings may have implications for the design of treatment modalities for tumor patients combining immunotherapeutic strategies and chemotherapy.
Abstract: Chemotherapy is an important treatment modality for many patients with advanced cancer. Recent data revealed that certain chemotherapeutic agents differentially affect maturation, cytokine production and T-cell stimulatory capacity of dendritic cells (DCs), which play a crucial role in the induction of antitumor immunity. Whereas most reports are based on mouse or human monocyte-derived DCs, studies investigating the direct effect of chemotherapeutic drugs on native human DCs are rather limited. Here, we evaluated the impact of various chemotherapeutic drugs on the immunostimulatory properties of 6-sulfo LacNAc+ (slan) DCs, representing a major subpopulation of human blood DCs. Because of their various antitumor effects, slanDCs may essentially contribute to the immune defense against tumors. We demonstrated that doxorubicin and vinblastine significantly impair the release of tumor necrosis factor-α, interleukin (IL)-6 and IL-12 by slanDCs. Functional data revealed that both drugs inhibit slanDC-mediated proliferation of T lymphocytes and their capacity to differentiate naive CD4+ T cells into proinflammatory T-helper type I cells. Furthermore, these agents markedly suppressed the ability of slanDCs to stimulate interferon-γ secretion by natural killer (NK) cells. In contrast, paclitaxel, mitomycin C and methotrexate sustained the ability of slanDCs to produce proinflammatory cytokines and their potential to activate T-lymphocytes and NK cells. These results indicate that doxorubicin and vinblastine impair the ability of native human DCs to stimulate important immune effector cells, whereas methotrexate, mitomycin C and paclitaxel maintain their immunostimulatory properties. These novel findings may have implications for the design of treatment modalities for tumor patients combining immunotherapeutic strategies and chemotherapy.
17 citations
TL;DR: It is found that both TLR7/8 agonists significantly improve the release of various proinflammatory cytokines by slanDCs and promote their tumor-directed cytotoxic activity.
14 citations
TL;DR: A novel modular targeting platform for T cell recruitment that not only efficiently replaces but also is superior to conventional T cell-engaging bispecific antibodies as it allows for the flexible targeting of several antigens and the delivery of co-stimulatory ligands to malignant lesions, thereby enhancing the antitumor potential of redirected T cells.
Abstract: We have recently described a novel modular targeting platform for T cell recruitment that not only efficiently replaces but also is superior to conventional T cell-engaging bispecific antibodies as it allows for the flexible targeting of several antigens and the delivery of co-stimulatory ligands to malignant lesions, thereby enhancing the antitumor potential of redirected T cells.
8 citations
TL;DR: Fibronectin, fibrillar collagen I, tropocollagen and collagen I/heparin maintain important immunosuppressive properties of MSCs, which support their suitablility as carriers for MSC transplants in tissue engineering.
Abstract: Mesenchymal stromal cells (MSCs) have emerged as promising candidates for regenerative therapies, including tissue engineering. Recently it has been reported that engineered extracellular matrix (ECM) components support the differentiation of MSCs into osteocytes and chondrocytes, indicating that ECM components may represent attractive carriers for MSC transplants to repair damaged tissues. However, little is known about the impact of engineered ECM components on the immunosuppressive properties of MSCs, which may essentially contribute to the prevention of allogeneic MSC transplant rejection. In the present study, we explored the potential of fibronectin, fibrillar collagen I, tropocollagen and collagen I/heparin to influence the immunosuppressive capacities of MSCs. We found that these ECM components do not modulate the capability of MSCs to inhibit the proliferation of anti-CD3/anti-CD28 antibody-stimulated CD4⁺ and CD8⁺ T cells and of lymphocytes in a mixed lymphocyte reaction. In addition, the potential of MSCs to impair the production of immunostimulatory IL-12 and to improve the release of immunosuppressive IL-10 by 6-sulpho LacNAc⁺ (slan) dendritic cells (DCs), representing a pro-inflammatory subset of human blood DCs, was not altered by the ECM components. Furthermore, ECM components do not influence the ability of MSCs to inhibit the slanDC-induced proliferation of CD4⁺ T cells. In conclusion, the used engineered ECMs maintain important immunosuppressive properties of MSCs, which support their suitablility as carriers for MSC transplants in tissue engineering.
6 citations
TL;DR: In vitro and in vivo data clearly underline that the combination of the established effector module with different target modules efficiently activated T cells against hematological malignancies.
Patent•
10 Sep 2013TL;DR: In this article, a braking device for a motor vehicle has a setpoint controlled deceleration device, which, upon receiving a braking request input by a driver or an assistance system, for example, on the basis of a difference between a set point value and an actual value, drives a brake of the vehicle to generate a set-point controlled braking torque for a decelerated motor vehicle.
Abstract: A braking device for a motor vehicle has a setpoint controlled deceleration device, which, upon receipt of a braking request input by a driver or an assistance system, for example, on the basis of a difference between a setpoint value and an actual value, drives a brake of the vehicle to generate a setpoint controlled braking torque for a deceleration of the motor vehicle. In addition, the braking device has a braking preparation control, which, upon receipt of a braking preparation signal, drives the brake independently of the setpoint value to produce at least one braking pressure for generating a preparation braking torque for a pre-deceleration of the motor vehicle. The braking preparation signal is generated as soon as a driving situation is ascertained where a braking request input by a driver or an assistance system is very likely imminent.
Patent•
11 Jul 2013
TL;DR: In this article, a tolerance range is defined by a tolerance band surrounding a specified target value, where the control or regulation of a driving power (p-g) takes place within the tolerance range further as a function of an actual maximum possible driving power of an electric machine.
Abstract: The method involves limiting the specification of a movement parameter (s-x,v-x,a-x) or the force or the moment by a tolerance range, where the control or regulation of a driving power (p-g) takes place within the tolerance range further as a function of an actual maximum possible driving power (p-el) of an electric machine (16). The tolerance range is defined by a tolerance band surrounding a specified target value. The driving power is provided within the tolerance range up to a power limit only by the electric machine. An independent claim is included for a controlling- or regulating device for controlling and regulating a driving power of a vehicle, particularly a motor vehicle.
Patent•
10 Sep 2013TL;DR: In this paper, a setpoint value-controlled deceleration device is proposed to actuate the brake of a motor vehicle on the basis of a difference between a target value and an actual value so as to generate a set point value controlled braking torque for a decelerated vehicle.
Abstract: A brake device and a method for actuating a brake device for a motor vehicle are described. The brake device has a setpoint value-controlled deceleration device which, for example upon receipt of a braking demand imparted by a driver or an assistance system, actuates a brake of the vehicle on the basis of a difference between a target value and an actual value so as to generate a setpoint value-controlled braking torque for a deceleration of the vehicle. Furthermore, the brake device has a brake preparation controller which, upon receipt of a brake preparation signal, actuates the brake independently of the target value so as to generate at least one brake pressure p1 for generating a preparatory braking torque for a significant pre-deceleration of the motor vehicle. Here, the brake preparation signal may be generated within the brake device or within an assistance system as soon as a driving situation is identified in which it can be expected with high probability that a braking demand will be imparted imminently by a driver or an assistance system. The brake device can in this way be prepared for a predictably imminently occurring braking demand, such that a braking torque which must then be generated can be generated quickly and with high precision. Furthermore, the preparatory braking torque can be generated slowly compared to a setpoint value-controlled braking torque, such that for example a hydraulic pump can be operated at relatively low rotational speeds and thus without excessive generation of noise.
Patent•
17 May 2013
TL;DR: Procede de commande et/ou de regulation en fonction d'au moins une consigne determinant la demande de freinage respective d'une installation de freins (38, 40, 42, 44) du vehicule (12) concerne un parametre de mouvement, une force, un couple (s, V, a, M, F ) as mentioned in this paper.
Abstract: Procede de commande et/ou de regulation en fonction d'au moins une consigne determinant la demande de freinage respective d'une installation de freins (38, 40, 42, 44) du vehicule (12) Cette consigne concerne un parametre de mouvement, une force, un couple (s , V , a , M, F ) Le vehicule (12) a une machine electrique (16) reliee a un accumulateur (36) pour servir d'installation de freins dynamique (38) et une autre installation de freins (40, 42, 44) On limite la consigne d'au moins un parametre de mouvement et/ou la force et/ou le couple (s , v , a , M, F ) par une plage de tolerance (Deltas , Deltav , Deltaa , DeltaF , DeltaM) La commande et/ou la regulation se fait dans la plage de tolerance (Deltas , Deltav , Deltaa , DeltaF , DeltaM) en fonction de la puissance de recuperation (P ) maximale possible de la machine electrique (16)
01 Jan 2013
TL;DR: This article discusses transplantation, neoplasia, and other topics related to organ donation and rejection which have been discussed in detail in the bloodjournal.org archives.
Abstract: http://bloodjournal.hematologylibrary.org/content/101/2/640.full.html Updated information and services can be found at: (1844 articles) Transplantation (4217 articles) Neoplasia Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: