Skip to main content

Table 1 Side effects of monoclonal Ab drugs caused by systemic on-target toxicity

From: Ab locks for improving the selectivity and safety of antibody drugs

mAb (Brand name; Company)

Target

Physiological distribution of target antigens

Indications

Selected adverse events

Refs

Adalimumab (Humira®; Abbott)/Infliximab (Remicade®; Janssen Biotech)

TNF-α

Activated macrophages, CD4+ T cells, NK cells, neutrophils, mast cells, eosinophils, and neurons

• Juvenilc idiopathic arthritis

• Crohn’s disease

• Ulcerative colitis

• Rheumatoid arthritis

• Ankylosing spondylitis

• Psoriatic arthritis

• Plaque psoriasis

• Anti-drug Ab (5%)

• Increased nuclear-specific antibodies (12%)

• Infections (e.g. 17% upper respiratory infection, increase 2-fold risk of tuberculosis)

• Increase 2-3-fold risk of malignancies (e.g. lymphoma and lymphoproliferative disorders)

• Anaemia, leukopaenia and thrombocytopaenia

• Immunosuppression

[111, 145, 146]

Natalizumab (Tysabri®; Biogen)

α4 integrin

Activated endothelial cells, CD8+ T cells, leukocytes

• Multiple sclerosis

• Infusion and hypersensitivity reactions (6%)

• Immunogenicity (6%)

• Progressive multifocal leukoencephalopathy (PML) (0.4%)

• Immunosuppression

• Hepatotoxicity

[18, 54, 81, 181]

Rituximab (Rituxan®; Genentech)

CD20

B cells

• Non-Hodgkin’s Lymphoma (NHL)

• Chronic Lymphocytic Leukemia (CLL)

• Rheumatoid arthritis

• Wegener’s Granulomatosis)

• Microscopic Polyangiitis (MPA)

• Infection (20%)

• Hepatitis B reactivation (8.7%)

• Immunosuppression

• Immunogenicity

• Renal toxicity

• CRS

• PML

[51, 171]

Efalizumab (Reptiva®; Genentech)

CD11a

B and T cells, monocytes, macrophages, neutrophils, basophils, and eosinophils

• Plaque psoriasis

• Malignancies (1.8%)

• Immune thrombocytopaenia (0.3%)

• Guillain–Barré syndrome, encephalitis, meningitis

• Immunosuppression

• Immune haemolytic anaemia

• PML

[6, 66, 147]

Alemtuzumab (Lemtrada®/Campath®; Genzyme)

CD52

B and T cells, monocytes, dendritic cells and mature sperm cells

• Multiple sclerosis

• CLL

• Kidney Transplantation

• Thyroid disorders (35%)

• Thrombocytopaenia (2%)

• Autoimmune neutropenia, haemolytic anaemia and autoimmune kidney diseases (0.3%)

• Lymphoproliferative disorders

• CRS

[13, 81, 137, 181]

Ipilimumab (Yervoy®; Bristol-Myers Squibb)

CTLA-4

Activated T cells, Treg

• Malignant Melanoma

• Renal Cell Carcinoma

• Metastatic Colorectal Cancer

• Colitis (11.1%)

• Severe skin reaction (6.5%)

• Hormone gland problems (especially the pituitary, adrenal, and thyroid glands)(4.6%)

• Enterocolitis (2.1%)

• Hepatitis (1.3%)

• Pneumonitis (1.22%)

[169]

Trastuzumab (Herceptin®; Genentech)

HER2

Cells derived from all three germ layer (e.g. epithelial cells, cardiomyocytes … )

• Metastatic Breast Cancer

• Metastatic Gastric Cancer

• Heart failure (2~7%)

• Cardiotoxicity (2.6~4.5%)

• Peripheral edema (5~10%)

• Hypertension (4%)

• Arrhythmia and palpitation (3%)

[30, 65, 69, 73, 85, 102, 116, 161]

Muromonab-CD3 (Orthoclone OKT3®; Centocor Ortho Biotech Products LP.)

CD3

CD4+ and CD8+ T cells

• Acute allograft rejection

• Acute graft-versus-host disease (GVHD)

• Flu-like syndrome (50%)

• Immunogenicity (3~61%)

• Central nervous system complications (3%)

• Immunosuppression and infections

• CRS

[37, 154]

  1. TNF-α tumor necrosis factor α, CD cluster of differentiation, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, HER2 human epidermal growth factor receptor 2, NK natural killer cell, Treg regulatory T cell, PML progressive multifocal leukoencephalopathy, CRS cytokine-released syndrome