Cytotoxicity of TGF alpha-PE40 and correlation to expression of epidermal growth factor receptor.
TGF alpha-PE40 is a chimeric protein composed of transforming growth factor alpha (TGF alpha) linked to a modified Pseudomonas exotoxin (PE40). We tested the in vitro cytotoxicity of TGF alpha-PE40 on 23 different solid human tumour xenografts established in nude mice and human bone marrow cells from healthy donors, utilising a modified clonogenic assay. In order to distinguish non-specific toxicity from the targeted effects of TGF alpha-PE40, epidermal growth factor receptor (EGFR) expression of the tumours studied was assessed by Northern blot, slot blot and immunohistochemistry. TGF alpha-PE40 demonstrated differential cytotoxicity on human tumour xenografts in the clonogenic assay. No toxicity on human bone marrow cells was observed. In vitro activity of TGF alpha-PE40 showed a significant correlation with the expression of EGF receptors as determined by immunohistochemistry and slot blot. Further studies will be performed in order to determine the in vivo activity of this compound in tumour-bearing nude mice.
Berger
D P
DP
Department of Internal Medicine I, Haematology/Oncology, University of Freiburg, Germany.
Herbstritt
L
L
Hellerich
U
U
Schulzke
S
S
Dengler
W A
WA
Gallo
M
M
Pastan
I
I
Mertelsmann
R
R
Fiebig
H H
HH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005098:Exotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D005098:Exotoxins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016211:Transforming Growth Factor alpha; C083452:transforming growth factor alpha-Pseudomonas exotoxin A (40); D066246:ErbB Receptors