Delivery and therapeutic potential of human granzyme B
Granzyme B (GzmB) is used by cytotoxic lymphocytes as a molecular weapon for the defense against virus-infected and malignantly transformed host cells. It belongs to a family of small serine proteases that are stored in secretory vesicles of killer cells. After secretion of these cytolytic granules...
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Published in | Immunological reviews Vol. 235; no. 1; pp. 159 - 171 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Oxford, UK : Blackwell Publishing Ltd
01.05.2010
Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Granzyme B (GzmB) is used by cytotoxic lymphocytes as a molecular weapon for the defense against virus-infected and malignantly transformed host cells. It belongs to a family of small serine proteases that are stored in secretory vesicles of killer cells. After secretion of these cytolytic granules during killer cell attack, GzmB is translocated into the cytosol of target cells with the help of the pore-forming protein perforin. GzmB has adopted similar protease specificity as caspase-8, and once delivered, it activates major executioner apoptosis pathways. Since GzmB is very effective in killing human tumor cell lines that are otherwise resistant against many cytotoxic drugs and since GzmB of human origin can be recombinantly expressed, its use as part of a 'magic bullet' in tumor therapy is a very tempting idea. In this review, we emphasize the peculiar characteristics of GzmB that make it suited for use as an effector domain in potential immunoconjugates. We discuss what is known about its uptake into target cells and the trials performed with GzmB-armed immunoconjugates, and we assess the prospects of its potential therapeutic value. |
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Bibliography: | http://dx.doi.org/10.1111/j.0105-2896.2010.00894.x ark:/67375/WNG-QKHXL2S9-1 istex:BDAF8D6369CDE7D2366D6EFF023E12B6F78586D8 ArticleID:IMR894 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0105-2896 1600-065X |
DOI: | 10.1111/j.0105-2896.2010.00894.x |