Search results for: Karl-Josef Kallen

Items from 1 to 20 out of 23 results

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A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer

Martin Sebastian, Andreas Schröder, Birgit Scheel, Henoch S. Hong, more

Cancer Immunology, Immunotherapy > 2019 > 68 > 5 > 799-812

CV9201 is an RNActive^®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal...

article

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

Alexandros Papachristofilou, Madeleine M. Hipp, Ute Klinkhardt, Martin Früh, more

Journal for ImmunoTherapy of Cancer > 2019 > 7 > 1 > 1-14

Background Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1),...

article

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, more

Journal for ImmunoTherapy of Cancer > 2016 > 4 > 1 > 1-106

article

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, more

Journal for ImmunoTherapy of Cancer > 2016 > 4 > 1 > 107-221

article

A new RNA-based adjuvant enhances virus-specific vaccine responses by locally activating DC and inducing IFN-I responses TLR- and RLH-dependently

Annett Keßler, Claudia Soldner, Stefan Lienenklaus, Julia Spanier, more

Cytokine > 2015 > 76 > 1 > 102

Among new adjuvants conferring a TH1-shift, RNAdjuvant® consisting of non-coding RNA complexed with a cationic carrier peptide is a promising candidate. Upon RNAdjuvant® treatment, bone marrow-derived myeloid dendritic cells (BM-mDC) and plasmacytoid DC (BM-pDC) showed Toll-like receptor (TLR)7-dependent IFN-I induction and upregulation of CD69 and CD86. This result was verified by the ex vivo analysis...

article

A novel RNA‐based adjuvant combines strong immunostimulatory capacities with a favorable safety profile

Regina Heidenreich, Edith Jasny, Aleksandra Kowalczyk, Johannes Lutz, more

International Journal of Cancer > 137 > 2 > 372 - 384

Protein‐ and peptide‐based tumor vaccines depend on strong adjuvants to induce potent immune responses. Here, we demonstrated that a recently developed novel adjuvant based on a non‐coding, long‐chain RNA molecule, termed RNAdjuvant^®, profoundly increased immunogenicity of both antigen formats. RNAdjuvant^® induced balanced, long‐lasting immune responses that resulted in a strong anti‐tumor activity...

article

Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study

Hubert Kübler, Birgit Scheel, Ulrike Gnad-Vogt, Kurt Miller, more

Journal for ImmunoTherapy of Cancer > 2015 > 3 > 1 > 1-14

Background CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. Methods 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts...

article

RNAdjuvant^®, a novel, highly-potent RNA-based adjuvant, combines strong immunostimulatory capacities with a favorable safety profile

Regina Heidenreich, Keyvan Tadjalli Mehr, Janine Noth, Sven Koch, more

Journal for ImmunoTherapy of Cancer > 2015 > 3 > 2 > 1-1

article

A randomized, double-blind, placebo-controlled, Phase I/II trial of RNActive^®-vaccine cv9104 in patients with metastatic castrate-refractory prostate cancer (mcrpc): first results of the Phase I part

Sven D Koch, Henoch Hong, Susan Feyerabend, Margitta Retz, more

Journal for ImmunoTherapy of Cancer > 2014 > 2 > 3 > 1-2

article

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect

Mariola Fotin‐Mleczek, Kai Zanzinger, Regina Heidenreich, Christina Lorenz, more

The Journal of Gene Medicine > 14 > 6 > 428 - 439

Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine‐complexed mRNA. Such two‐component mRNA vaccines support both antigen expression and immune stimulation. These self‐adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune...

article

Inhibition of Interleukin-6-Transsignaling via gp130-Fc in Hemorrhagic Shock and Sepsis

Soeren Torge Mees, Sietje Toellner, Kerstin Marx, Fred Faendrich, more

Journal of Surgical Research > 2009 > 157 > 2 > 235-242

Immune function after hemorrhagic shock and subsequent sepsis is characterized by an early proinflammatory burst of IL-6, and high IL-6 levels have been linked to high mortality after trauma and in sepsis. Trans-signaling is defined as the activation of cells that do not express the membrane bound IL-6 receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc is able to bind...

article

IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier

Ralf A. Linker, Fred Lühder, Karl-Josef Kallen, De-Hyung Lee, more

Journal of Neuroimmunology > 2008 > 205 > 1-2 > 64-72

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It exerts its cellular effects by a membrane-bound IL-6 receptor (IL-6R), or, alternatively, by forming a complex with the soluble IL-6R (sIL-6R), a process named IL-6 transsignalling. Here we investigate the role of IL-6 transsignalling in myelin basic protein (MBP)-induced EAE in the...

article

gp130 dimerization in the absence of ligand: Preformed cytokine receptor complexes

Stephanie Tenhumberg, Björn Schuster, Lixin Zhu, Marina Kovaleva, more

Biochemical and Biophysical Research Communications > 2006 > 346 > 3 > 649-657

It is established that cytokine receptors signal after ligand binding as homo- or hetero-dimers in heteromeric complexes, but it is unclear, when dimerization occurs. To investigate gp130 dimerization, we performed co-precipitation experiments with the endogenous cytokine receptors gp130 and leukemia inhibitory factor receptor (LIF-R) and with gp130 variants carrying two different C-terminal peptide...

article

Targeting MUC1 with liposomal BLP25

Martin H. Falk, Karl-Josef Kallen

EJC Supplements > 2006 > 4 > 6 > 12-13

article

Development of a monoclonal antibody-based enzyme-linked immunoabsorbent assay for the binding of gp130 to the IL-6/IL-6R complex and its competitive inhibition

Jürgen Scheller, Marina Kovaleva, Björn Rabe, Jutta Eichler, more

Journal of Immunological Methods > 2004 > 291 > 1-2 > 93-100

The proinflammatory cytokine IL-6 binds to the membrane bound or soluble IL-6 receptor (IL-6R) and activates an intracellular signaling cascade after complex formation with two gp130 molecules. These mediate general homeostasis and orchestrates the immune response during disease. Trans-signalling via the soluble IL-6R has importance for the development and maintenance of human diseases like Crohn's...

article

Lack of gp130 expression in hepatocytes promotes liver injury1 1 K.L.S. and T.W. contributed equally to this work.

Konrad L StreetZ, Torsten Wüstefeld, Christian Klein, Karl-Josef Kallen, more

Gastroenterology > 2003 > 125 > 2 > 532-543

Interleukin 6 (IL-6) contributes via its signal transducer gp130 to the acute phase response (APR) in hepatocytes. Recent studies indicated that IL-6 is involved in the regulation of different pathophysiologic conditions of the liver. To define the IL-6-dependent intracellular pathways more specifically, we generated a hepatocyte-specific gp130 knockout mouse. Hepatocyte-specific gp130-deficient...

article

Analysis of the Leukemia Inhibitory Factor Receptor Functional Domains by Chimeric Receptors and Cytokines ^†

Dorthe Aasland, Björn Schuster, Joachim Grötzinger, Stefan Rose-John, more

Biochemistry > 2003 > 42 > 18 > 5244 - 5252

article

The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane

Björn Schuster, Werner Meinert, Stefan Rose-John, Karl-Josef Kallen

FEBS Letters > 2003 > 538 > 1-3 > 113-116

The recently solved X-ray structure of the extracellular portion of the interleukin-6 (IL-6) receptor (IL-6R) revealed an IL-6R dimer in the crystal lattice which probably represents a physiological dimer. Performing coprecipitation experiments with two differently tagged IL-6R variants expressed in COS-7 cells, we show that an IL-6R dimer exists in the plasma membrane in the absence of IL-6. Ligand...

article

The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases

Karl-Josef Kallen

BBA - Molecular Cell Research > 2002 > 1592 > 3 > 323-343

The activation of cells that do not express the membrane bound interleukin-6 6 receptor (IL-6R) by IL-6 and the soluble IL-6 receptor (sIL-6R) is termed transsignalling. Transsignalling may be an pathogenetic factor in human diseases as diverse as multiple myeloma (MM), Castleman's disease, prostate carcinoma, Crohn's disease, systemic sclerosis, Still's disease, osteoporosis and cardiovascular diseases...

article

The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex11Edited by M. Yaniv

Dorthe Aasland, Birgit Oppmann, Joachim Grötzinger, Stefan Rose-John, more

Journal of Molecular Biology > 2002 > 315 > 4 > 637-646

To elucidate the function of the two cytokine-binding modules (CBM) of the leukemia inhibitory factor receptor (LIFR), receptor chimeras of LIFR and the interleukin-6 receptor (IL-6R) were constructed. Either the NH₂-terminal (chimera RILLIFΔI) or the COOH-terminal LIFR CBM (chimera RILLIFΔII) were replaced by the structurally related CBM of the IL-6R which does not bind LIF. Chimera RILLIFΔI is functionally...

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Search results for: Karl-Josef Kallen

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

A new RNA-based adjuvant enhances virus-specific vaccine responses by locally activating DC and inducing IFN-I responses TLR- and RLH-dependently

A novel RNA‐based adjuvant combines strong immunostimulatory capacities with a favorable safety profile

Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study

RNAdjuvant^®, a novel, highly-potent RNA-based adjuvant, combines strong immunostimulatory capacities with a favorable safety profile

A randomized, double-blind, placebo-controlled, Phase I/II trial of RNActive^®-vaccine cv9104 in patients with metastatic castrate-refractory prostate cancer (mcrpc): first results of the Phase I part

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect

Inhibition of Interleukin-6-Transsignaling via gp130-Fc in Hemorrhagic Shock and Sepsis

IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier

gp130 dimerization in the absence of ligand: Preformed cytokine receptor complexes

Targeting MUC1 with liposomal BLP25

Development of a monoclonal antibody-based enzyme-linked immunoabsorbent assay for the binding of gp130 to the IL-6/IL-6R complex and its competitive inhibition

Lack of gp130 expression in hepatocytes promotes liver injury1 1 K.L.S. and T.W. contributed equally to this work.

Analysis of the Leukemia Inhibitory Factor Receptor Functional Domains by Chimeric Receptors and Cytokines ^†

The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane

The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases

The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex11Edited by M. Yaniv

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