Abstract |
The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor-alpha ( TGF alpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/ TGF alpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/ TGF alpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/ TGF alpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/ TGF alpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers.
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Authors | C P Theuer, D J FitzGerald, I Pastan |
Journal | The Journal of urology
(J Urol)
Vol. 149
Issue 6
Pg. 1626-32
(Jun 1993)
ISSN: 0022-5347 [Print] United States |
PMID | 8501821
(Publication Type: Journal Article)
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Chemical References |
- Bacterial Toxins
- Exotoxins
- Immunotoxins
- Recombinant Fusion Proteins
- Recombinant Proteins
- Transforming Growth Factor alpha
- Virulence Factors
- transforming growth factor(alpha)-Pseudomonas exotoxin A (35)
- ADP Ribose Transferases
- Pseudomonas aeruginosa exotoxin A
- ErbB Receptors
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Topics |
- ADP Ribose Transferases
- Bacterial Toxins
(therapeutic use)
- Drug Design
- Drug Screening Assays, Antitumor
- ErbB Receptors
(drug effects)
- Exotoxins
(therapeutic use)
- Humans
- Immunotoxins
(therapeutic use)
- In Vitro Techniques
- Pseudomonas aeruginosa
- Recombinant Fusion Proteins
- Recombinant Proteins
(therapeutic use)
- Transforming Growth Factor alpha
(therapeutic use)
- Urinary Bladder Neoplasms
(chemistry, therapy)
- Virulence Factors
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