In vitro sensitivity testing of human bladder cancers and cell lines to TP-40, a hybrid protein with selective targeting and cytotoxicity

J Urol. 1993 Dec;150(6):1950-5. doi: 10.1016/s0022-5347(17)35944-x.

Abstract

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.

MeSH terms

  • ADP Ribose Transferases*
  • Animals
  • Bacterial Toxins / pharmacology*
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / analysis
  • Exotoxins / pharmacology*
  • Humans
  • Immunotoxins / therapeutic use*
  • In Vitro Techniques
  • Mice
  • Pseudomonas aeruginosa
  • Recombinant Fusion Proteins / pharmacology*
  • Transforming Growth Factor alpha / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / drug therapy*
  • Virulence Factors*

Substances

  • Bacterial Toxins
  • Exotoxins
  • Immunotoxins
  • Recombinant Fusion Proteins
  • Transforming Growth Factor alpha
  • Virulence Factors
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa
  • ErbB Receptors