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
T2  - 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
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/12007
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-120078
VL  - 5
ER  -