dc.contributor.author |
Pereira, Jennifer |
en |
dc.contributor.author |
Hill-Cawthorne, GA |
en |
dc.contributor.author |
Lin, A |
en |
dc.contributor.author |
Zandi, MS |
en |
dc.contributor.author |
McCarthy, C |
en |
dc.contributor.author |
Jones, JL |
en |
dc.contributor.author |
Willcox, M |
en |
dc.contributor.author |
Shaw, D |
en |
dc.contributor.author |
Thompson, SA |
en |
dc.contributor.author |
Compston, AS |
en |
dc.contributor.author |
Hale, G |
en |
dc.contributor.author |
Waldmann, H |
en |
dc.contributor.author |
Coles, AJ |
en |
dc.coverage.spatial |
United States |
en |
dc.date.accessioned |
2012-03-12T20:56:58Z |
en |
dc.date.issued |
2010-07-01 |
en |
dc.identifier.citation |
Journal of Immunology 185(1):763-768 01 Jul 2010 |
en |
dc.identifier.issn |
0022-1767 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/14002 |
en |
dc.description.abstract |
Biological therapies, even humanized mAbs, may induce antiglobulin responses that impair efficacy. We tested a novel strategy to induce tolerance to a therapeutic mAb. Twenty patients with relapsing-remitting multiple sclerosis received an initial cycle of alemtuzumab (Campath-1H), up to 120 mg over 5 d, preceded by 500 mg SM3. This Ab differs from alemtuzumab by a single point mutation and is designed not to bind to cells. Twelve months later, they received a second cycle of alemtuzumab, up to 72 mg over 3 d. One month after that, 4 of 19 (21%) patients had detectable serum anti-alemtuzumab Abs compared with 145 of 197 (74%) patients who received two cycles of alemtuzumab without SM3 in the phase 2 CAMMS223 trial (p < 0.001). The efficacy and safety profile of alemtuzumab was unaffected by SM3 pretreatment. Long-lasting "high-zone" tolerance to a biological therapy may be induced by pretreatment with a high i.v. dose of a drug variant, altered to reduce target-binding. |
en |
dc.language |
eng |
en |
dc.publisher |
The American Association of Immunologists, Inc. |
en |
dc.relation.ispartofseries |
Journal of Immunology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0022-1767/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Adolescent |
en |
dc.subject |
Adult |
en |
dc.subject |
Amino Acid Substitution |
en |
dc.subject |
Antibodies, Anti-Idiotypic |
en |
dc.subject |
Antibodies, Monoclonal |
en |
dc.subject |
Antibodies, Monoclonal, Humanized |
en |
dc.subject |
Antibodies, Neoplasm |
en |
dc.subject |
Dose-Response Relationship, Immunologic |
en |
dc.subject |
Drug Administration Schedule |
en |
dc.subject |
Female |
en |
dc.subject |
Humans |
en |
dc.subject |
Immune Tolerance |
en |
dc.subject |
Magnetic Resonance Imaging |
en |
dc.subject |
Male |
en |
dc.subject |
Multiple Sclerosis, Relapsing-Remitting |
en |
dc.subject |
Pilot Projects |
en |
dc.subject |
Point Mutation |
en |
dc.subject |
Randomized Controlled Trials as Topic |
en |
dc.subject |
Treatment Outcome |
en |
dc.subject |
Young Adult |
en |
dc.title |
A novel strategy to reduce the immunogenicity of biological therapies. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.4049/jimmunol.1000422 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
763 |
en |
pubs.volume |
185 |
en |
dc.rights.holder |
Copyright: The American Association of Immunologists, Inc. |
en |
dc.identifier.pmid |
20519651 |
en |
pubs.end-page |
768 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
198840 |
en |
dc.identifier.eissn |
1550-6606 |
en |
dc.identifier.pii |
jimmunol.1000422 |
en |
pubs.record-created-at-source-date |
2012-02-20 |
en |
pubs.dimensions-id |
20519651 |
en |