PMID- 24092811
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20201226
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 13
IP  - 1
DP  - 2014 Jan
TI  - Tetravalent antibody-scTRAIL fusion proteins with improved properties.
PG  - 101-11
LID - 10.1158/1535-7163.MCT-13-0396 [doi]
AB  - We applied the immunoglobulin E (IgE) heavy-chain domain 2 (EHD2) as the 
      covalently linked homodimerization module to generate antibody-scTRAIL fusion 
      proteins. By fusing a humanized single-chain fragment variable (scFv) directed 
      against EGFR to the N-terminus of the EHD2 and a single-chain derivative of TRAIL 
      (scTRAIL) to the C-terminus of the EHD2, we produced a dimeric, tetravalent 
      fusion protein. The fusion protein retained its binding activity for EGFR and 
      TRAIL receptors. In vitro, the targeted antibody-scTRAIL fusion protein exhibited 
      an approximately 8- to 18-fold increased cytotoxic activity compared with the 
      untargeted EHD2-scTRAIL fusion protein. This resulted in increased antitumor 
      activity in a subcutaneous Colo205 xenograft tumor murine model. In summary, the 
      scFv-EHD2-scTRAIL fusion protein combines target cell selectivity with an 
      increased TRAIL activity leading to improved antitumor activities.
FAU - Seifert, Oliver
AU  - Seifert O
AD  - Corresponding Author: Roland E. Kontermann, Institut fur Zellbiologie und 
      Immunologie, Universitat Stuttgart, Allmandring 31, 70569 Stuttgart, Germany. 
      roland.kontermann@izi.uni-stuttgart.de.
FAU - Plappert, Aline
AU  - Plappert A
FAU - Fellermeier, Sina
AU  - Fellermeier S
FAU - Siegemund, Martin
AU  - Siegemund M
FAU - Pfizenmaier, Klaus
AU  - Pfizenmaier K
FAU - Kontermann, Roland E
AU  - Kontermann RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131003
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Single-Chain Antibodies)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Apoptosis/genetics/immunology
MH  - Cell Line, Tumor
MH  - ErbB Receptors/genetics/immunology
MH  - Humans
MH  - Immunoglobulin E/genetics/immunology/*pharmacology
MH  - Mice
MH  - Neoplasms/genetics/*immunology/therapy
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/immunology
MH  - Recombinant Fusion Proteins/immunology/pharmacology
MH  - Single-Chain Antibodies/genetics/immunology/*pharmacology
MH  - TNF-Related Apoptosis-Inducing Ligand/*genetics/immunology
MH  - Xenograft Model Antitumor Assays
EDAT- 2013/10/05 06:00
MHDA- 2014/09/30 06:00
CRDT- 2013/10/05 06:00
PHST- 2013/10/05 06:00 [entrez]
PHST- 2013/10/05 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
AID - 1535-7163.MCT-13-0396 [pii]
AID - 10.1158/1535-7163.MCT-13-0396 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2014 Jan;13(1):101-11. doi: 10.1158/1535-7163.MCT-13-0396. Epub 
      2013 Oct 3.