Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity.
IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in m...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4503742?pdf=render |
| _version_ | 1818621311853789184 |
|---|---|
| author | Lena Winstedt Sofia Järnum Emma Andersson Nordahl Andreas Olsson Anna Runström Robert Bockermann Christofer Karlsson Johan Malmström Gabriella Samuelsson Palmgren Ulf Malmqvist Lars Björck Christian Kjellman |
| author_facet | Lena Winstedt Sofia Järnum Emma Andersson Nordahl Andreas Olsson Anna Runström Robert Bockermann Christofer Karlsson Johan Malmström Gabriella Samuelsson Palmgren Ulf Malmqvist Lars Björck Christian Kjellman |
| author_sort | Lena Winstedt |
| collection | DOAJ |
| description | IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions.ClinicalTrials.gov NCT01802697. |
| first_indexed | 2024-12-16T18:07:16Z |
| format | Article |
| id | doaj.art-6f6ac6ca824a4f8190c70a48251951d2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T18:07:16Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6f6ac6ca824a4f8190c70a48251951d22022-12-21T22:21:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013201110.1371/journal.pone.0132011Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity.Lena WinstedtSofia JärnumEmma Andersson NordahlAndreas OlssonAnna RunströmRobert BockermannChristofer KarlssonJohan MalmströmGabriella Samuelsson PalmgrenUlf MalmqvistLars BjörckChristian KjellmanIdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions.ClinicalTrials.gov NCT01802697.http://europepmc.org/articles/PMC4503742?pdf=render |
| spellingShingle | Lena Winstedt Sofia Järnum Emma Andersson Nordahl Andreas Olsson Anna Runström Robert Bockermann Christofer Karlsson Johan Malmström Gabriella Samuelsson Palmgren Ulf Malmqvist Lars Björck Christian Kjellman Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. PLoS ONE |
| title | Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. |
| title_full | Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. |
| title_fullStr | Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. |
| title_full_unstemmed | Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. |
| title_short | Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. |
| title_sort | complete removal of extracellular igg antibodies in a randomized dose escalation phase i study with the bacterial enzyme ides a novel therapeutic opportunity |
| url | http://europepmc.org/articles/PMC4503742?pdf=render |
| work_keys_str_mv | AT lenawinstedt completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT sofiajarnum completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT emmaanderssonnordahl completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT andreasolsson completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT annarunstrom completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT robertbockermann completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT christoferkarlsson completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT johanmalmstrom completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT gabriellasamuelssonpalmgren completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT ulfmalmqvist completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT larsbjorck completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity AT christiankjellman completeremovalofextracellulariggantibodiesinarandomizeddoseescalationphaseistudywiththebacterialenzymeidesanoveltherapeuticopportunity |