Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer: Challenges and opportunities

Nirmala @ Chandralega Kampan, Sue D. Xiang, Orla M. McNally, Andrew N. Stephens, Michael A. Quinn, Magdalena Plebanski

Research output: Contribution to journalReview article

11 Citations (Scopus)

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 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 immuno-therapies, 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.

Original languageEnglish
Pages (from-to)4785-4806
Number of pages22
JournalCurrent Medicinal Chemistry
Volume25
Issue number36
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Interleukin-6 Receptors
Interleukin-6
Neoplasms
Therapeutics
Cytokine Receptor gp130
Chemotherapy
Kidney Neoplasms
Tumors
Multiple Myeloma
Ovarian Neoplasms
Immunotherapy
Stabilization
Monoclonal Antibodies
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Cytokines
Chronic Disease
Clinical Trials
Drug Therapy

Keywords

  • Cancer
  • IL-6
  • IL-6 receptor
  • Immunotherapy
  • JAK-STAT signalling pathway
  • Monoclonal antibodies
  • Pro-inflammatory cytokine
  • STAT-3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer : Challenges and opportunities. / Kampan, Nirmala @ Chandralega; Xiang, Sue D.; McNally, Orla M.; Stephens, Andrew N.; Quinn, Michael A.; Plebanski, Magdalena.

In: Current Medicinal Chemistry, Vol. 25, No. 36, 01.01.2018, p. 4785-4806.

Research output: Contribution to journalReview article

Kampan, Nirmala @ Chandralega ; Xiang, Sue D. ; McNally, Orla M. ; Stephens, Andrew N. ; Quinn, Michael A. ; Plebanski, Magdalena. / Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer : Challenges and opportunities. In: Current Medicinal Chemistry. 2018 ; Vol. 25, No. 36. pp. 4785-4806.
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