Journal
JOURNAL OF IMMUNOLOGY
Volume 185, Issue 1, Pages 763-768Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000422
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Funding
- Moulton Charitable Foundation
- Medical Research Council
- National Institute for Health Research Biomedical Research Centre, Cambridge
- Multiple Sclerosis International Federation
- Neurological Foundation of New Zealand
- Medical Research Council [G1000215] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10335, CL-2008-14-004] Funding Source: researchfish
- MRC [G1000215] Funding Source: UKRI
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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. The Journal of Immunology, 2010, 185: 763-768.
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