Biologics (1) Tumor Necrosis Factor Inhibitors 生物制剂之肿瘤坏死因子抑制剂

What is “biologic” agent?

Whole immune system suppression will cause serious side effects. Therefore “biologic” agents are developed to target partial immune systems for a variety of immune-mediated skin disorders, including psoriasis, atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, urticaria, and cutaneous B-cell lymphomas as well as the cutaneous manifestations of systemic conditions such as Crohn disease, sarcoidosis, and vasculitis.

Tumor Necrosis Factor TNF

Tumour Necrosis Factor is a protein produced by macrophages/monocytes and T lymphocytes [1]. The human TNFα are located on chromosome 6p21.33. Plasma TNF Normal value < or = 2.8 pg/mL,  Serum TNF-alpha normal value < or = 5.6 pg/mL [2]

The macrophages/monocytes and T lymphotcytes are kinds of immune system white blood cells, they locate and ‘eat’ harmful particles such as bacteria, viruses, fungi, and parasites.

TNF (normal value) regulate a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation[3,4]. It may boost a person’s immune response, and also may cause necrosis (cell death) of some types of tumor cells [5].

Depleted TNF (below normal value) may induce tuberculosis infection, bacterial infection, virus infections, breast cancer, lung cancer, lymphoma, and skin cancer [1,4].

Elevated TNF (above normal value) may induce psoriasis, rheumatoid arthritis (RA), inflammatory bowel diseases including Crohn’s disease and ulcerative colitis, multiple sclerosis, systemic lupus erythematosus and systemic sclerosis [1,4].

Tumor Necrosis Factor Inhibitor

The FDA has approved multiple tumor necrosis factor (TNF; previously known as TNF-α) inhibitors: etanercept (Enbrel ® ), etanerceptszzs (ErelziTM ), infliximab (Remicade ® ), infliximab-dyyb (Inflectra ® ), adalimumab (Humira ® ), adalimumab-atto (Amjevita ® ), golimumab (Simponi ® ), and certolizumab pegol (Cimzia ® ) [6].

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US Food and Drug Administration (FDA) warnings and precautions for targeted immune modulators with dermatologic indications. Live vaccines should not be given to patients receiving these medications. BCG, bacillus Calmette–Guérin; IL, interleukin; LE, lupus erythematosus; TNF, tumor necrosis factor [6].

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Nomenclature for monoclonal antibodies and fusion proteins. For example, ada-lim-u-mab, inf-li-xi-mab and certo-li-zu-mab pegol are immunomodulating immunoglobulins that are human, chimeric and humanized, respectively [6].

 

Reference:

    1. Mayo Clinic Laboratory. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/63022
    2. tumor necrosis factor [Homo sapiens (human)] Gene ID: 7124, updated on 11-Nov-2019. https://www.ncbi.nlm.nih.gov/gene/7124
    3. Tumor necrosis factor (TNF) Gene 19116 Online Mendelian Inheritance in Man. https://omim.org/entry/191160
    4. Definition of tumor necrosis factor. National Cancer Institue. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-necrosis-factor
    5. Jean L. Bolognia , Julie V. Schaffer , Lorenzo Cerroni, edit. Dermatology, Fourth edition, China: Elsevier, 2018, ISBN 978–0‐7020–6275–9. page2244-2250