摘要
白细胞介素-6(IL-6)是一种众所周知的促炎细胞因子,具有多向性作用,是包括癌症在内的慢性炎症性疾病的中心因子。因此,阻断IL-6信号通路已成为治疗多中心Castleman病、多发性骨髓瘤和肾、前列腺、肺、结直肠癌和卵巢癌等多种肿瘤的靶点。抗IL-6单克隆抗体(Siltuximab)和抗IL-6受体(Tocilizumab)的单克隆抗体(Tocilizumab,Tocilizumab)已成为单独或联合常规化疗的潜在免疫治疗方法。人类试验已经证明了阻断IL-6活性和多中心CD的能力,从而导致持久的临床反应和更长的疾病稳定。然而,这些治疗方法对其他癌症的疗效仍有争议。在发展中的新一代治疗药物如Clazakizumab、Sarilumab和可溶性gp 130-FC具有更高的结合亲和力、更好的特异性和较低的副作用。深入了解这些药物的免疫学基础,以及免疫治疗产品在临床试验中所面临的挑战,将有助于选择最有希望的抗IL-6/IL-6的治疗方法大规模使用。同时,目前针对个性化治疗的研究工作可能有助于从IL-6阻断疗法中获益的患者的治疗。
关键词: IL-6,IL-6受体,促炎细胞因子,免疫治疗,单克隆抗体,癌症,STAT-3,JAK-STAT信号通路.
Current Medicinal Chemistry
Title:Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities
Volume: 25 Issue: 36
关键词: IL-6,IL-6受体,促炎细胞因子,免疫治疗,单克隆抗体,癌症,STAT-3,JAK-STAT信号通路.
摘要: Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signalling pathway has become a target for the therapy of diverse cancers such as multicentric Castleman’s disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy. Human trials have demonstrated the ability to block IL-6 activity and in multicentric CD lead to durable clinical response and longer disease stabilisation. However, the efficacy of these treatments is still debatable for other cancers. New generation therapeutics in development such as Clazakizumab, Sarilumab, and soluble gp130-Fc have the additional features of improved binding affinity, better specificity with reduced adverse effects. A deeper understanding of the immunological basis of these agents, as well as of the challenges that are faced by immunotherapy-based products in clinical trials, will help select the most promising anti-IL-6/IL-6R therapies for large scale use. Concurrently, current research efforts to personalize treatments may help in the treatment of patients that would greatly benefit from IL-6 blocking therapies.
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Cite this article as:
Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities, Current Medicinal Chemistry 2018; 25 (36) . https://dx.doi.org/10.2174/0929867324666170712160621
DOI https://dx.doi.org/10.2174/0929867324666170712160621 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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