Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line

Int J Cancer. 1996 Feb 8;65(4):485-90. doi: 10.1002/(SICI)1097-0215(19960208)65:4<485::AID-IJC16>3.0.CO;2-9.

Abstract

Immunotoxins were prepared by linking the type 1 ribosome-inactivating proteins (RIP) momordin I, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6 to the 48-127 monoclonal antibody (MAb) recognising a glycoprotein (gp54) expressed on all human bladder tumours tested and on human bladder carcinoma cell lines, in particular on the T24 cell line. T24 cells required a 2 hr contact with immunotoxins to ensure binding and endocytosis. A time course of exposure, followed by further incubation without the immunotoxins, showed that maximum inhibition of protein synthesis by T24 cells was reached after 2 hr of contact followed by 3 days without the immunotoxins. Under optimal conditions, 48-127/RIP immunotoxins at nanomolar concentrations inhibited by 50% protein synthesis of target T24 cells. No toxicity was observed if (i) target cells were treated with non-conjugated RIP, (ii) target cells were treated with momordin I- or PAP-S-containing immunotoxins made with an irrelevant antibody and (iii) a non-target cell line was treated with the same 2 RIP conjugated to 48-127 antibody. The in vitro selective toxicity of these immunotoxins encourages further studies in view of a possible use in clinical trials for the local therapy of human bladder carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunotoxins / pharmacology*
  • N-Glycosyl Hydrolases*
  • Plant Proteins / pharmacology*
  • Protein Biosynthesis
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • Ribosomes / drug effects*
  • Saporins
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Immunotoxins
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • momordin I (protein)
  • N-Glycosyl Hydrolases
  • Saporins
  • pokeweed antiviral protein