Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.

<h4>Background</h4>We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner.<h4>Methodology/principal findings</h4>Optical imaging of uptake kinetics...

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Autores principales:	Mathias Gehrmann, Stefan Stangl, Andreas Kirschner, Gemma A Foulds, Wolfgang Sievert, Brigitte T Doss, Axel Walch, Alan G Pockley, Gabriele Multhoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bbe5931322b0429783f0f82fe2648265
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spelling	oai:doaj.org-article:bbe5931322b0429783f0f82fe26482652021-11-18T07:11:48ZImmunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.1932-620310.1371/journal.pone.0041341https://doaj.org/article/bbe5931322b0429783f0f82fe26482652012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22829941/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner.<h4>Methodology/principal findings</h4>Optical imaging of uptake kinetics revealed co-localization of grB with recycling endosomes (Rab9/11) as early as 5 min after internalization, with late endosomes (Rab7) after 30 min, and the lysosomal compartment (LAMP1/2) after 60 to 120 min. Active caspase-3-mediated apoptosis was induced in mouse CT26 monolayer cells and 3D tumor spheroids, but not in normal mouse endothelial cells. Granzyme B selectively reduced the proportion of membrane Hsp70-positive cells in CT26 tumor spheroids. Consecutive i.v. injections of recombinant human grB into mice bearing membrane Hsp70-positive CT26 tumors resulted in significant tumor suppression, and a detailed inspection of normal mouse organs revealed that the administration of anti-tumoral concentrations of grB elicited no clinicopathological changes.<h4>Conclusions/significance</h4>These findings support the future clinical evaluation of human grB as a potential adjuvant therapeutic agent, especially for treating immunosuppressed patients that bear membrane Hsp70-positive tumors.Mathias GehrmannStefan StanglAndreas KirschnerGemma A FouldsWolfgang SievertBrigitte T DossAxel WalchAlan G PockleyGabriele MulthoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41341 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mathias Gehrmann Stefan Stangl Andreas Kirschner Gemma A Foulds Wolfgang Sievert Brigitte T Doss Axel Walch Alan G Pockley Gabriele Multhoff Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
description	<h4>Background</h4>We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner.<h4>Methodology/principal findings</h4>Optical imaging of uptake kinetics revealed co-localization of grB with recycling endosomes (Rab9/11) as early as 5 min after internalization, with late endosomes (Rab7) after 30 min, and the lysosomal compartment (LAMP1/2) after 60 to 120 min. Active caspase-3-mediated apoptosis was induced in mouse CT26 monolayer cells and 3D tumor spheroids, but not in normal mouse endothelial cells. Granzyme B selectively reduced the proportion of membrane Hsp70-positive cells in CT26 tumor spheroids. Consecutive i.v. injections of recombinant human grB into mice bearing membrane Hsp70-positive CT26 tumors resulted in significant tumor suppression, and a detailed inspection of normal mouse organs revealed that the administration of anti-tumoral concentrations of grB elicited no clinicopathological changes.<h4>Conclusions/significance</h4>These findings support the future clinical evaluation of human grB as a potential adjuvant therapeutic agent, especially for treating immunosuppressed patients that bear membrane Hsp70-positive tumors.
format	article
author	Mathias Gehrmann Stefan Stangl Andreas Kirschner Gemma A Foulds Wolfgang Sievert Brigitte T Doss Axel Walch Alan G Pockley Gabriele Multhoff
author_facet	Mathias Gehrmann Stefan Stangl Andreas Kirschner Gemma A Foulds Wolfgang Sievert Brigitte T Doss Axel Walch Alan G Pockley Gabriele Multhoff
author_sort	Mathias Gehrmann
title	Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
title_short	Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
title_full	Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
title_fullStr	Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
title_full_unstemmed	Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.
title_sort	immunotherapeutic targeting of membrane hsp70-expressing tumors using recombinant human granzyme b.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/bbe5931322b0429783f0f82fe2648265
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Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B.

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