Killing of target cells by redirected granzyme B in the absence of perforin

FEBS Lett. 2004 Mar 26;562(1-3):87-92. doi: 10.1016/S0014-5793(04)00187-5.


Granzyme B (GzmB) is a potent apoptosis-inducing serine protease of cytotoxic lymphocytes. Following receptor-mediated endocytosis, GzmB is supposed to enter the cytosol through perforin-mediated membrane disruption. We investigated whether retargeting of GzmB to Lewis Y positive surface receptors could lead to perforin-independent target cell death. We coupled recombinant GzmB to the Lewis Y-binding antibody dsFv-B3. Targeting of GzmB to Lewis Y positive cells triggered cell death with similar efficacy as dsFv-B3 targeted Pseudomonas exotoxin fragment 38 (PE38). Since GzmB was only weakly inhibited by plasma proteins, GzmB-based immunoconjugates should be useful as a new class of immunotoxins with low immunogenicity utilizing programmed cell death for therapeutic purposes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Bacterial Toxins / immunology
  • Bacterial Toxins / metabolism
  • Cell Line
  • Granzymes
  • Humans
  • Lewis Blood Group Antigens / genetics
  • Lewis Blood Group Antigens / immunology
  • Lewis Blood Group Antigens / metabolism
  • Membrane Glycoproteins / metabolism*
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Cell Surface / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism


  • Bacterial Toxins
  • Lewis Blood Group Antigens
  • Lewis Y antigen
  • Membrane Glycoproteins
  • Peptide Fragments
  • Pore Forming Cytotoxic Proteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases