A novel strategy to reduce the immunogenicity of biological therapies.

Journal of immunology (Baltimore, Md. : 1950) (2010-06-04)
Jennifer Somerfield, Grant A Hill-Cawthorne, Andrew Lin, Michael S Zandi, Claire McCarthy, Joanne L Jones, Michael Willcox, David Shaw, Sara A J Thompson, Alastair S Compston, Geoff Hale, Herman Waldmann, Alasdair J Coles
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
TWEEN® 20, viscous liquid
Sigma-Aldrich
ExtrAvidin®−Peroxidase, buffered aqueous solution