title: Non-depleting anti-CD4 monoclonal antibody induces immune tolerance to ERT in a murine model of Pompe disease.
abstract: Approximately 35-40% of patients with classic infantile Pompe disease treated with enzyme replacement therapy (ERT) develop high, sustained antibody titers against the therapeutic enzyme alglucosidase alfa, which abrogates the treatment efficacy. Induction of antigen-specific immune tolerance would greatly enhance ERT for these patients. Here we show that a short-course treatment with non-depleting anti-CD4 monoclonal antibody successfully induced long-term ERT-specific immune tolerance in Pompe disease mice. Our data suggest an effective adjuvant therapy to ERT.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Baodong
authors.initials: B
authors.lastname: Sun
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Suhrad G
authors.initials: SG
authors.lastname: Banugaria
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sean N
authors.initials: SN
authors.lastname: Prater
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Trusha T
authors.initials: TT
authors.lastname: Patel
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Fredrickson
authors.affiliation: Tolerx, Inc., Cambridge, MA, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ringler
authors.affiliation: Tolerx, Inc., Cambridge, MA, USA.
authors.forename: Antonin
authors.initials: A
authors.lastname: de Fougerolles
authors.affiliation: Division of Therapeutic Proteins, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Rosenberg
authors.affiliation: Sir William Dunn School of Pathology, Oxford University, Oxford, UK.
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
keywords: Anti-CD4 antibody; Antigen-specific immune tolerance; CRIM, cross-reacting immunologic material; ERT, enzyme replacement therapy; Enzyme replacement therapy; GAA, acid-α-glucosidase; IPD, infantile Pompe disease; ITI, immune tolerance induction; MTX, methotrexate; Pompe disease