Dr Nirmala Kampan and Dr Sue Xiang
This article reviews the current research, clinical trials and clinical practise in immunotherapies targeting interleukin 6 (IL-6) or IL-6 receptors (IL-6R) as monotherapy or in combination as treatments for multiple tumor types, such as multiple myeloma, renal, prostate, lung, colorectal, ovarian cancers etc, as well as multicentric castleman’s disease. IL-6 is a well-known pro-inflammatory cytokine with pleiotropic activity and a central player in chronic inflammatory diseases including cancers. IL-6 plays an essential and physiological role in virtually every organ system. 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. This review provides a comprehensive overview and a better understanding of the immunological basis of those agents, and challenges faced by immunotherapy- based products in clinical trials.
Centre for Cancer Research
Ovarian Cancer Biomarker Laboratory
Journal and article title
As a pleiotropic cytokine, IL-6 and its dysregulation is clearly evident in various cancers. Although anti-IL-6 or anti-IL-6R monotherapies have been effective in most of the clinical trials conducted in chronic inflammatory and autoimmune disease cohorts, those agents have not exhibited significant anti-tumor activity. However, in combination with conventional chemotherapy or other therapeutic agents, anti-IL-6 or anti-IL-6R therapies show enhanced efficacy initially but neither durable responses nor improvement in prognosis and survival. A possible explanation may be that tumour cell clones with the ability to evade immune system or alternative growth factors other than IL-6 continue to proliferate unchecked.
This review provides a comprehensive overview and a better understanding of the immunological basis of anti-IL-6 or anti-IL-6R immunotherapies. Of a range of different monoclonal antibody agents against IL-6 and IL-6R, Siltuximab and Tocilizumab are the most promising immunotherapies as both have demonstrated favourable clinical response and minimal toxicities in various basic and clinical studies reviewed so far. Both these agents should be further studied in a larger sample of patients in immunotherapy-focused clinical trials. Furthermore, understanding of the difference in challenges faced by immunotherapy agents compared to conventional chemotherapy drugs will help to facilitate identifying a subset of patients who will most likely benefit from anti-IL-6 or anti-IL-6R therapies.
Chronic inflammatory diseases including cancers, such as multicentric castleman's disease, multiple myeloma and solid tumors including renal, prostate, lung, colorectal and ovarian cancers.