A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells

FEBS Lett. 2002 Apr 10;516(1-3):208-12. doi: 10.1016/s0014-5793(02)02527-9.

Abstract

We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor, and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far, overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new, potentially attractive anticancer agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Gene Expression
  • Genes, erbB-2*
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / genetics
  • Immunoconjugates / pharmacology*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Ribonucleases / chemistry
  • Ribonucleases / genetics
  • Ribonucleases / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Immunoconjugates
  • Recombinant Fusion Proteins
  • Receptor, ErbB-2
  • Ribonucleases