Biological Immunosuppressants 免疫生物制剂

Biological immunosuppressants, often called biologics, represent a more advanced category of immunosuppressive agents. They are isolated from a variety of natural sources – human, animal, or microorganism and are designed to suppress specific pathways or molecules in the immune system with precision.

Key Types and Mechanisms of Biological Immunosuppressants

1. Tumor Necrosis Factor (TNF) Inhibitors

  • Infliximab (Remicade): for rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.
  • Adalimumab (Humira): for rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.
  • Etanercept (Enbrel): for rheumatoid arthritis, psoriasis, and ankylosing spondylitis.
  • Golimumab (Simponi): for rheumatoid arthritis, ankylosing spondylitis, and ulcerative colitis.
  • Certolizumab pegol (Cimzia): for Crohn’s disease and rheumatoid arthritis.

2. Interleukin IL Inhibitors

  • Dupilumab (Dupixent) : Anti-IL-4/IL-13, for atopic dermatitis, asthma
  • Tocilizumab (Actemra): Inhibits IL-6; for rheumatoid arthritis.
  • Secukinumab (Cosentyx): Blocks IL-17A, for psoriasis and ankylosing spondylitis.
  • Ustekinumab (Stelara): Blocks IL-12 and IL-23; for psoriasis and Crohn’s disease.
  • Ixekizumab (Taltz): Inhibits IL-17A; for psoriasis.
  • Anakinra (Kineret): Inhibits IL-1, for rheumatoid arthritis.

3. B-Cell Inhibitors

  • Rituximab (Rituxan): Inhibits CD20 on B-cells; for rheumatoid arthritis, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia.
  • Belimumab (Benlysta): Inhibits B-cell activating factor (BAFF); for lupus.

4. T-Cell Inhibitors

  • Abatacept (Orencia): Binds to CD80 and CD86 on antigen-presenting cells to prevent T-cell activation; for rheumatoid arthritis.
  • Alefacept (Amevive): Inhibits CD2 on T-cells; for psoriasis.

5. Calcineurin Inhibitors. Inhibit calcineurin, reducing T-cell activity.

  • Cyclosporine (Neoral, Gengraf): for organ transplantation, psoriasis, and rheumatoid arthritis.
  • Tacrolimus (Prograf, Protopic): for organ transplantation, dermatitis, and psoriasis.

6. Selective Adhesion Molecule Inhibitors. Prevent immune cells from migrating to areas of inflammation, particularly effective in gastrointestinal disorders.

  • Natalizumab (Tysabri): Blocks α4-integrin; treats multiple sclerosis and Crohn’s disease.
  • Vedolizumab (Entyvio): Blocks α4β7 integrin; used for ulcerative colitis and Crohn’s disease.

7. Janus Kinase (JAK) Inhibitors. Inhibit the JAK-STAT pathway involved in immune cell signalling.

  • Tofacitinib (Xeljanz): for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.
  • Baricitinib (Olumiant): for rheumatoid arthritis and under investigation for other conditions.
  • Upadacitinib (Rinvoq): or rheumatoid arthritis.

8. mTOR Inhibitors Inhibit mTOR (mammalian target of rapamycin). Inhibit cell growth and immune response.

  • Sirolimus (Rapamune): for organ rejection, particularly kidney transplants.
  • Everolimus (Zortress): for organ transplantation and some cancers.

Reference

  1. Hussain Y, Khan H. Immunosuppressive Drugs. Encyclopedia of Infection and Immunity. 2022:726–40. doi: 10.1016/B978-0-12-818731-9.00068-9. Epub 2022 Apr 8. PMCID: PMC8987166.
  2. Maria Meneghini, Oriol Bestard, Josep Maria Grinyo. Immunosuppressive drugs modes of action. Best Practice & Research Clinical Gastroenterology
    Volumes 54–55, October–December 2021, 101757

生物免疫抑制剂(也称为生物制剂)代表着一类更先进的免疫抑制药物。它们从多种天然来源(人类、动物或微生物)中分离得到,旨在精确抑制免疫系统中的特定通路或分子。

生物免疫抑制剂的主要类型和作用机制:

  1. 肿瘤坏死因子(TNF)抑制剂
  • 英夫利西单抗(Remicade):用于类风湿性关节炎、克罗恩病和溃疡性结肠炎。
  • 阿达木单抗(Humira):用于类风湿性关节炎、银屑病、克罗恩病和溃疡性结肠炎。
  • 依那西普(Enbrel):用于类风湿性关节炎、银屑病和强直性脊柱炎。
  • 戈利木单抗(Simponi):用于类风湿性关节炎、强直性脊柱炎和溃疡性结肠炎。
  • 培塞利珠单抗(Cimzia):用于克罗恩病和类风湿性关节炎。
  1. 白细胞介素(IL)抑制剂
  • 度普利尤单抗(Dupixent):抗IL-4/IL-13,用于特应性皮炎、哮喘
  • 托珠单抗(Actemra):抑制IL-6;用于类风湿性关节炎。
  • 司库奇尤单抗(Cosentyx):阻断IL-17A,用于银屑病和强直性脊柱炎。
  • 乌司奴单抗(Stelara):阻断IL-12和IL-23;用于银屑病和克罗恩病。
  • 依奇珠单抗(Taltz):抑制IL-17A;用于银屑病。
  • 阿那白滞素(Kineret):抑制IL-1,用于类风湿性关节炎。
  1. B细胞抑制剂
  • 利妥昔单抗(Rituxan):抑制B细胞上的CD20;用于类风湿性关节炎、非霍奇金淋巴瘤和慢性淋巴细胞白血病。
  • 贝利木单抗(Benlysta):抑制B细胞激活因子(BAFF);用于狼疮。
  1. T细胞抑制剂
  • 阿巴西普(Orencia):与抗原呈递细胞上的CD80和CD86结合以防止T细胞激活;用于类风湿性关节炎。
  • 阿法西普(Amevive):抑制T细胞上的CD2;用于银屑病。
  1. 钙调磷酸酶抑制剂。抑制钙调磷酸酶,减少T细胞活性。
  • 环孢素(Neoral, Gengraf):用于器官移植、银屑病和类风湿性关节炎。
  • 他克莫司(Prograf, Protopic):用于器官移植、皮炎和银屑病。
  1. 选择性粘附分子抑制剂。防止免疫细胞迁移到炎症区域,特别适用于胃肠道疾病。
  • 那他珠单抗(Tysabri):阻断α4-整合素;治疗多发性硬化症和克罗恩病。
  • 维多珠单抗(Entyvio):阻断α4β7整合素;用于溃疡性结肠炎和克罗恩病。
  1. JAK激酶抑制剂。抑制参与免疫细胞信号传导的JAK-STAT通路。
  • 托法替尼(Xeljanz):用于类风湿性关节炎、银屑病性关节炎和溃疡性结肠炎。
  • 巴利替尼(Olumiant):用于类风湿性关节炎,其他适应症正在研究中。
  • 乌帕替尼(Rinvoq):用于类风湿性关节炎。
  1. mTOR抑制剂 抑制mTOR(哺乳动物雷帕霉素靶蛋白)。抑制细胞生长和免疫反应。
  • 西罗莫司(Rapamune):用于器官排斥,特别是肾移植。
  • 依维莫司(Zortress):用于器官移植和某些癌症。