A novel strategy to reduce the immunogenicity of biological therapies.
J Immunol
; 185(1): 763-8, 2010 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-20519651
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.
Texto completo:
1
Eixos temáticos:
Pesquisa_clinica
Base de dados:
MEDLINE
Assunto principal:
Esclerose Múltipla Recidivante-Remitente
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Tolerância Imunológica
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Anticorpos Monoclonais
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Anticorpos Antineoplásicos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article