A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients.

ABSTRACT: Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)^1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation^3,4. To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supp

SUBMITTER: Cassotta A 

PROVIDER: S-EPMC6795539 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature