TY  - JOUR
A1  - Schilbach, Karin
A1  - Alkhaled, Mohammed
A1  - Welker, Christian
A1  - Eckert, Franziska
A1  - Blank, Gregor
A1  - Ziegler, Hendrik
A1  - Sterk, Marco
A1  - Müller, Friederike
A1  - Sonntag, Katja
A1  - Wieder, Thomas
A1  - Braumüller, Heidi
A1  - Schmitt, Julia
A1  - Eyrich, Matthias
A1  - Schleicher, Sabine
A1  - Seitz, Christian
A1  - Erbacher, Annika
A1  - Pichler, Bernd J.
A1  - Müller, Hartmut
A1  - Tighe, Robert
A1  - Lim, Annick
A1  - Gillies, Stephen D.
A1  - Strittmatter, Wolfgang
A1  - Röcken, Martin
A1  - Handgretinger, Rupert
T1  - Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation
JF  - OncoImmunology
N2  - Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.
KW  - TH17 cells
KW  - cancer-targeted IL-12
KW  - differentiation
KW  - humanized mice
KW  - immunocytokine
KW  - immunotherapy
KW  - M1/M2 macrophages
KW  - rhabdomyosarcoma
KW  - TH1-induced senescence
KW  - tumor-infiltrating lymphocytes
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154579
VL  - 4
IS  - 7
ER  - 
TY  - JOUR
A1  - Schleicher, Bernd
A1  - Arbet-Engels, Axel
A1  - Baack, Dominik
A1  - Balbo, Matteo
A1  - Biland, Adrian
A1  - Blank, Michael
A1  - Bretz, Thomas
A1  - Bruegge, Kai
A1  - Bulinski, Michael
A1  - Buss, Jens
A1  - Doerr, Manuel
A1  - Dorner, Daniela
A1  - Elsaesser, Dominik
A1  - Grischagin, Sergej
A1  - Hildebrand, Dorothee
A1  - Linhoff, Lena
A1  - Mannheim, Karl
A1  - Mueller, Sebastian Achim
A1  - Neise, Dominik
A1  - Neronov, Andrii
A1  - Noethe, Maximilian
A1  - Paravac, Aleksander
A1  - Rhode, Wolfgang
A1  - Schulz, Florian
A1  - Sedlaczek, Kevin
A1  - Shukla, Amit
A1  - Sliusar, Vitalii
A1  - Willert, Elan
A1  - Walter, Roland
T1  - Fractional Variability—A Tool to Study Blazar Variability
JF  - Galaxies
N2  - Active Galactic Nuclei emit radiation over the whole electromagnetic spectrum up to TeV energies. Blazars are one subtype with their jets pointing towards the observer. One of their typical features is extreme variability on timescales, from minutes to years. The fractional variability is an often used parameter for investigating the degree of variability of a light curve. Different detection methods and sensitivities of the instruments result in differently binned data and light curves with gaps. As they can influence the physics interpretation of the broadband variability, the effects of these differences on the fractional variability need to be studied. In this paper, we study the systematic effects of completeness in time coverage and the sampling rate. Using public data from instruments monitoring blazars in various energy ranges, we study the variability of the bright TeV blazars Mrk 421 and Mrk 501 over the electromagnetic spectrum, taking into account the systematic effects, and compare our findings with previous results. Especially in the TeV range, the fractional variability is higher than in previous studies, which can be explained by the much longer (seven years compared to few weeks) and more complete data sample.
KW  - blazars
KW  - variability
KW  - fractional variability
KW  - active galactic nuclei
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197348
SN  - 2075-4434
VL  - 7
IS  - 2
ER  -