Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses

Maria D.F.S. Barbosa, Esteban Celis

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of MHC class II binding epitopes to helper T cells (CD4+ T cells) and subsequent B cell activation. DCs, CD4+ T cells and MHC class II binding epitopes are also involved in self-tolerance. While many assay formats are available for reliable antibody detection, the complex in vivo interplay between immunogenicity and tolerance hinders accurate pre-clinical predictions of protein drug immunogenicity to humans.

Original languageEnglish (US)
Pages (from-to)674-681
Number of pages8
JournalDrug Discovery Today
Volume12
Issue number15-16
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Fingerprint

Dendritic Cells
Antibody Formation
Epitopes
Immunoglobulin Class Switching
T-Lymphocytes
Self Tolerance
Immunoglobulin Isotypes
Helper-Inducer T-Lymphocytes
Neutralizing Antibodies
Pharmaceutical Preparations
Proteins
B-Lymphocytes
Immunoglobulin G
Safety
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses. / Barbosa, Maria D.F.S.; Celis, Esteban.

In: Drug Discovery Today, Vol. 12, No. 15-16, 01.08.2007, p. 674-681.

Research output: Contribution to journalReview article

@article{0243f9dab2e24943be153b043a702754,
title = "Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses",
abstract = "Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of MHC class II binding epitopes to helper T cells (CD4+ T cells) and subsequent B cell activation. DCs, CD4+ T cells and MHC class II binding epitopes are also involved in self-tolerance. While many assay formats are available for reliable antibody detection, the complex in vivo interplay between immunogenicity and tolerance hinders accurate pre-clinical predictions of protein drug immunogenicity to humans.",
author = "Barbosa, {Maria D.F.S.} and Esteban Celis",
year = "2007",
month = "8",
day = "1",
doi = "10.1016/j.drudis.2007.06.005",
language = "English (US)",
volume = "12",
pages = "674--681",
journal = "Drug Discovery Today",
issn = "1359-6446",
publisher = "Elsevier Limited",
number = "15-16",

}

TY - JOUR

T1 - Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses

AU - Barbosa, Maria D.F.S.

AU - Celis, Esteban

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of MHC class II binding epitopes to helper T cells (CD4+ T cells) and subsequent B cell activation. DCs, CD4+ T cells and MHC class II binding epitopes are also involved in self-tolerance. While many assay formats are available for reliable antibody detection, the complex in vivo interplay between immunogenicity and tolerance hinders accurate pre-clinical predictions of protein drug immunogenicity to humans.

AB - Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of MHC class II binding epitopes to helper T cells (CD4+ T cells) and subsequent B cell activation. DCs, CD4+ T cells and MHC class II binding epitopes are also involved in self-tolerance. While many assay formats are available for reliable antibody detection, the complex in vivo interplay between immunogenicity and tolerance hinders accurate pre-clinical predictions of protein drug immunogenicity to humans.

UR - http://www.scopus.com/inward/record.url?scp=34547743906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547743906&partnerID=8YFLogxK

U2 - 10.1016/j.drudis.2007.06.005

DO - 10.1016/j.drudis.2007.06.005

M3 - Review article

C2 - 17706550

AN - SCOPUS:34547743906

VL - 12

SP - 674

EP - 681

JO - Drug Discovery Today

JF - Drug Discovery Today

SN - 1359-6446

IS - 15-16

ER -