A RECOMBINANT FORM OF PSEUDOMONAS EXOTOXIN A CONTAINING TRANSFORMING GROWTH FACTOR-ALPHA NEAR ITS CARBOXYL-TERMINUS FOR THE TREATMENT OF BLADDER-CANCER

作者：THEUER CP; FITZGERALD DJ; PASTAN I

来源：Journal of Urology, 1993, 149(6): 1626-1632.

• BLADDER NEOPLASMS
• IMMUNOTOXINS
• RECEPTORS-EPIDERMAL GROWTH FACTOR-UROGASTRONE

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 (TGFalpha) 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/TGFalpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGFalpha-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/TGFalpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGFalpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers.

• 出版日期1993-6