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Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation.

Oncoimmunology (2015-07-04)
Karin Schilbach, Mohammed Alkhaled, Christian Welker, Franziska Eckert, Gregor Blank, Hendrik Ziegler, Marco Sterk, Friederike Müller, Katja Sonntag, Thomas Wieder, Heidi Braumüller, Julia Schmitt, Matthias Eyrich, Sabine Schleicher, Christian Seitz, Annika Erbacher, Bernd J Pichler, Hartmut Müller, Robert Tighe, Annick Lim, Stephen D Gillies, Wolfgang Strittmatter, Martin Röcken, Rupert Handgretinger
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium iodide, 99.999% trace metals basis
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IL-2 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
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Interleukin-2 human, recombinant, expressed in E. coli, ~10000 U/mL
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Sodium iodide, AnhydroBeads, −10 mesh, 99.999% trace metals basis
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IL-2 human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)