Archivum Immunologiae et Therapiae Experimentalis

, Volume 60, Issue 5, pp 331–344

Immunogenicity to Biologics: Mechanisms, Prediction and Reduction

  • Swaminathan Sethu
  • Karthik Govindappa
  • Mohammad Alhaidari
  • Munir Pirmohamed
  • Kevin Park
  • Jean Sathish
Review

DOI: 10.1007/s00005-012-0189-7

Cite this article as:
Sethu, S., Govindappa, K., Alhaidari, M. et al. Arch. Immunol. Ther. Exp. (2012) 60: 331. doi:10.1007/s00005-012-0189-7

Abstract

Currently, there is a significant rise in the development and clinical use of a unique class of pharmaceuticals termed as Biopharmaceuticals or Biologics, in the management of a range of disease conditions with, remarkable therapeutic benefits. However, there is an equally growing concern regarding development of adverse effects like immunogenicity in the form of anti-drug antibodies (ADA) production and hypersensitivity. Immunogenicity to biologics represents a significant hurdle in the continuing therapy of patients in a number of disease settings. Efforts focussed on the identification of factors that contribute towards the onset of immunogenic response to biologics have led to reductions in the incidence of immunogenicity. An in-depth understanding of the cellular and molecular mechanism underpinning immunogenic responses will likely improve the safety profile of biologics. This review addresses the mechanistic basis of ADA generation to biologics, with emphasis on the role of antigen processing and presentation in this process. The article also addresses the potential contribution of complement system in augmenting or modulating this response. Identifying specific factors that influences processing and presentation of biologic-derived antigens in different genotype and disease background may offer additional options for intervention in the immunogenic process and consequently, the management of immunogenicity to biologics.

Keywords

BiologicsImmunogenicityAntigen processingComplement

Abbreviations

ADA

Anti-drug antibody

APC

Antigen-presenting cells

BAb

Binding antibody

BCR

B cell receptor

BMP7

Bone morphogenetic protein-7

C1q

Complement component 1q

C3a

Complement factor 3a

C3aR

Complement 3a receptor

C3d

Complement factor 3d

C5a

Complement factor 5a

CD

Cluster of differentiation

CpG

Deoxy-cytidylate-phosphate-deoxy-guanylate

DCs

Dendritic cells

EGFR

Epidermal growth factor receptor

FcγR

Fc gamma receptor

GH

Growth hormone

GHRH

Growth-hormone-releasing hormone

GM-CSF

Granulocyte macrophage colony stimulating factor

GnRH

Gonadotrophin-releasing hormone

HIV

Human immunodeficiency virus

HLA

Human leukocyte antigen

HPV

Human papilloma virus

IFN

Interferon

Ig

Immunoglobulin

IL

Interleukin

LFA

Lymphocyte function-associated antigen

LPS

Lipopolysaccharides

mAb

Monoclonal antibody

MHC

Major histocompatibility complex

NAb

Neutralizing antibody

PDGF

Platelet-derived growth factor

PEG

Polyethylene glycol

PSA

Prostate-specific antigen

Rh

Rhesus factor

Td

T cell-dependent

Th

T helper cells

Ti

T cell-independent

TAG-72

Tumor-associated glycoprotein 72

TLR

Toll-like receptor

TNFα

Tumor necrosis factor alpha

Tregs

T regulatory cells

VEGF

Vascular endothelial growth factor

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012

Authors and Affiliations

  • Swaminathan Sethu
    • 1
  • Karthik Govindappa
    • 1
  • Mohammad Alhaidari
    • 1
  • Munir Pirmohamed
    • 1
  • Kevin Park
    • 1
  • Jean Sathish
    • 1
  1. 1.MRC Centre for Drug Safety Science and Department of Molecular and Clinical PharmacologyUniversity of LiverpoolLiverpoolUK