In vitro sensitivity testing of human bladder cancers and cell lines to TP-40, a hybrid protein with selective targeting and cytotoxicity.
TP-40 is a hybrid fusion protein produced by recombinant technology and consists of a molecule of transforming growth factor-alpha (TGF-alpha) fused to the Pseudomonas exotoxin PE-40. A panel of human and murine bladder cancer cell lines was found to be universally sensitive in vitro to TP-40 in a clonogenic assay. All lines expressed receptor for epidermal growth factor (EGF), though none demonstrated gene amplification for the EGF receptor. The sensitivity to TP-40 may be blocked by preexposure to EGF. Six human bladder tumors taken directly from patients were all sensitive in vitro to TP-40; these included well-differentiated tumors. TP-40 may prove to be effective as an intravesical agent in bladder cancer via selective targeting to cells that express EGF receptors, as do the majority of human bladder cancers.
Sarosdy
M F
MF
Division of Urology and Oncology, University of Texas Health Science Center, San Antonio 78284-7845.
Hutzler
D H
DH
Yee
D
D
von Hoff
D D
DD
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000032:analysis; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D051379:Mice; D011550:Pseudomonas aeruginosa; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D066246:ErbB Receptors; D005098:Exotoxins; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A