scholarly journals Pseudomonas exotoxin A mutants. Replacement of surface exposed residues in domain II with cysteine residues that can be modified with polyethylene glycol in a site-specific manner.

1994 ◽  
Vol 269 (10) ◽  
pp. 7610-7616
Author(s):  
C.T. Kuan ◽  
Q.C. Wang ◽  
I. Pastan
2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Byeong Sung Lee ◽  
Yumi Lee ◽  
Jisoo Park ◽  
Bo Seok Jeong ◽  
Migyeong Jo ◽  
...  

1986 ◽  
Vol 261 (24) ◽  
pp. 11404-11408 ◽  
Author(s):  
Z T Farahbakhsh ◽  
R L Baldwin ◽  
B J Wisnieski

2013 ◽  
Vol 95 (2) ◽  
pp. 742-751 ◽  
Author(s):  
Hsin-Ping Yang ◽  
Tsan-Chih Wang ◽  
Shiou-Jen Wang ◽  
Shih-Ping Chen ◽  
Eva Wu ◽  
...  

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 753
Author(s):  
Alexandra Fischer ◽  
Isis Wolf ◽  
Hendrik Fuchs ◽  
Anie Priscilla Masilamani ◽  
Philipp Wolf

The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of the natural ligand EGF as binding domain and PE40, the natural toxin domain of Pseudomonas Exotoxin A, or PE24mut, the de-immunized variant thereof, as toxin domains. Both targeted toxins were expressed in the periplasm of E.coli and evoked an inhibition of protein biosynthesis in EGFR-expressing PCa cells. Concentration- and time-dependent killing of PCa cells was found with IC50 values after 48 and 72 h in the low nanomolar or picomolar range based on the induction of apoptosis. EGF-PE24mut was found to be about 11- to 120-fold less toxic than EGF-PE40. Both targeted toxins were more than 600 to 140,000-fold more cytotoxic than the EGFR inhibitor erlotinib. Due to their high and specific cytotoxicity, the EGF-based targeted toxins EGF-PE40 and EGF-PE24mut represent promising candidates for the future treatment of PCa.


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