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Killing of target cells by redirected granzyme B in the absence of perforin.
- Source :
-
FEBS letters [FEBS Lett] 2004 Mar 26; Vol. 562 (1-3), pp. 87-92. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- 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
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
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
Membrane Glycoproteins metabolism
Serine Endopeptidases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-5793
- Volume :
- 562
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 15044006
- Full Text :
- https://doi.org/10.1016/S0014-5793(04)00187-5