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Immunogenicity to Biologics: Mechanisms, Prediction and Reduction

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

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.

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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

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  1. MRC Centre for Drug Safety Science and Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, L69 3GE, UK

    Swaminathan Sethu, Karthik Govindappa, Mohammad Alhaidari, Munir Pirmohamed, Kevin Park & Jean Sathish

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  1. Swaminathan Sethu
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Correspondence to Jean Sathish.

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Sethu, S., Govindappa, K., Alhaidari, M. et al. Immunogenicity to Biologics: Mechanisms, Prediction and Reduction. Arch. Immunol. Ther. Exp. 60, 331–344 (2012). https://doi.org/10.1007/s00005-012-0189-7

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