Journal
FEBS LETTERS
Volume 562, Issue 1-3, Pages 87-92Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(04)00187-5
Keywords
granzyme B; apoptosis; immunotoxin; Lewis Y; tumor
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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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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