Immunotherapeutic Interleukin-6 or Interleukin-6 receptor blockade in cancer: challenges and opportunities.

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Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M

Immunotherapeutic Interleukin-6 or Interleukin-6 receptor blockade in cancer: challenges and opportunities.

Curr Med Chem. 2017 Jul 12. doi: 10.2174/0929867324666170712160621.

PubMed ID

28707587 [ View in PubMed

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Abstract

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 signaling pathway has become a target for the therapy of in 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 gp130Fc has 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 treatment of patients that would greatly benefit from IL-6 blocking therapies.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sarilumab	Interleukin-6 receptor subunit alpha	Protein	Humans	Yes	Antagonist Antibody	Details