TY  - JOUR
A1  - El-Mesery, M.
A1  - Trebing, J.
A1  - Schafer, V.
A1  - Weisenberger, D.
A1  - Siegmund, D.
A1  - Wajant, H.
T1  - CD40-directed scFv-TRAIL fusion proteins induce CD40-restricted tumor cell death and activate dendritic cells
JF  - Cell Death & Disease
N2  - Targeted cancer therapy concepts often aim at the induction of adjuvant antitumor immunity or stimulation of tumor cell apoptosis. There is further evidence that combined application of immune stimulating and tumor apoptosis-inducing compounds elicits a synergistic antitumor effect. Here, we describe the development and characterization of bifunctional fusion proteins consisting of a single-chain variable fragment (scFv) domain derived from the CD40-specific monoclonal antibody G28-5 that is fused to the N-terminus of stabilized trimeric soluble variants of the death ligand TNF-related apoptosis-inducing ligand (TRAIL). As shown before by us and others for other cell surface antigen-targeted scFv-TRAIL fusion proteins, scFv:G28-TRAIL displayed an enhanced capacity to induce apoptosis upon CD40 binding. Studies with scFv:G28 fusion proteins of TRAIL mutants that discriminate between the two TRAIL death receptors, TRAILR1 and TRAILR2, further revealed that the CD40 binding-dependent mode of apoptosis induction of scFv:G28-TRAIL is operable with each of the two TRAIL death receptors. Binding of scFv:G28-TRAIL fusion proteins to CD40 not only result in enhanced TRAIL death receptor signaling but also in activation of the targeted CD40 molecule. In accordance with the latter, the scFv:G28-TRAIL fusion proteins triggered strong CD40-mediated maturation of dendritic cells. The CD40-targeted TRAIL fusion proteins described in this study therefore represent a novel type of bifunctional fusion proteins that couple stimulation of antigen presenting cells and apoptosis induction.
KW  - dendritic cells
KW  - apoptosis
KW  - CD40
KW  - TRAIL
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128777
VL  - 4
IS  - e916
ER  - 
TY  - JOUR
A1  - Fischer, D.
A1  - Weisenberger, D.
A1  - Scheer, Ulrich
T1  - In situ hybridization of DIG-labeled rRNA probes to mouse liver ultrathin sections
N2  - No abstract available.
KW  - Hybridisierung <Biologie>
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69458
ER  - 
TY  - JOUR
A1  - Trebing, J.
A1  - El-Mesery, M.
A1  - Schäfer, V.
A1  - Weisenberger, D.
A1  - Siegmund, D.
A1  - Silence, K.
A1  - Wajant, H.
T1  - CD70-restricted specific activation of TRAILR1 or TRAILR2 using scFv-targeted TRAIL mutants
JF  - Cell Death & Disease
N2  - To combine the CD27 stimulation inhibitory effect of blocking CD70 antibodies with an antibody-dependent cellular cytotoxicity (ADCC)-independent, cell death-inducing activity for targeting of CD70-expressing tumors, we evaluated here fusion proteins of the apoptosis-inducing TNF family member TRAIL and a single-chain variable fragment (scFv) derived from a high-affinity llama-derived anti-human CD70 antibody (lαhCD70). A fusion protein of scFv:lαhCD70 with TNC-TRAIL, a stabilized form of TRAIL, showed strongly enhanced apoptosis induction upon CD70 binding and furthermore efficiently interfered with CD70-CD27 interaction. Noteworthy, introduction of recently identified mutations that discriminate between TRAILR1 and TRAILR2 binding into the TRAIL part of scFv:lαhCD70-TNC-TRAIL resulted in TRAIL death receptor-specific fusion proteins with CD70-restricted activity.
KW  - apoptosis
KW  - CD27
KW  - CD70
KW  - scFv
KW  - TRAIL
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120078
VL  - 5
ER  -