BRINKMANN, Ulrich,GERG, Michael,STAHL, Sebastian,NIEDERFELLNER, Gerhard,DUCRET, Axel,PASTAN, Ira H.
申请号：
EPEP2016/064629
公开号：
WO2016/207324A1
申请日:
2016.06.23
申请国别(地区):
WO
年份:
2016
代理人:
摘要：
The invention is based on the finding that cells containing eukaryotic elongation factor 2 (eEF2) that lacks the diphthamide modification at the His715 residue remain sensitive to killing by PE when the cells also contain eEF2 with the diphthamide modification at the His715 residue. Accordingly, the invention provides methods for assessing sensitivity and/or resistance of diseased cells in a patient to treatment with a NAD (+) −diphthamide ADP-ribosyltransferase, the method comprising assaying for the presence of eEF2 protein having diphthamide modification at the His715 residue in a sample containing the diseased cells, wherein the presence of eEF2 protein having diphthamide modification at the His715 residue is indicative that the diseased cells are sensitive to treatment with a NAD (+) −diphthamide ADP-ribosyltrans ferase and/or wherein the absence of eEF2 protein having diphthamide modification at the His715 residue is indicative that the diseased cells are resistant to treatment with a NAD (+) −diphthamide ADP-ribosyltransferase. Also provided are NAD (+) −diphthamide ADP ribosylatransferases for use in methods of medical treatment, monoclonal anti-eEF2 antibodies, methods for assessing increased sensitivity of diseased cells in a patient to treatment with TNFα or other inducer of NFkappaB-signalling pathways or related signalling pathways and TNFα or other inducers for use in methods of medical treatment.Linvention se base sur la découverte que des cellules contenant le facteur 2 délongation eucaryote (eEF2) qui ne présente pas la modification du diphtamide au niveau du résidu His715 restent sensibles à la destruction par PE lorsque les cellules contiennent également le facteur eEF2 présentant la modification du diphtamide au niveau du résidu His715. Par conséquent, linvention concerne des procédés permettant dévaluer la sensibilité et/ou la résistance de cellules malades chez un patient à un traitement avec une NAD(+)-diphtamide ADP-ribosyl-transférase, le pr
